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RECOGNIZING AND TREATING ANXIETY AND DEPRESSION IN ADOLESCENTS
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RECOGNIZING AND TREATING ANXIETY AND DEPRESSION IN ADOLESCENTS Normal and Abnormal Responses Alya Reeve, MD
The vicissitudes of adolescence often make an individual question his or her own sanity. Extremes of emotion are not uncommon; however, prolonged states of an emotional extreme and abrupt changes in patterns of usual behavior are indicators of abnormal processes. Anxiety is a normal physiologic and psychologic response to change in or around an individual. Signal anxiety occurs normally to alert the individual that there is something not right with the environment-that a potential danger exists. This arousing of the defense system, toward a fight-or-fight response, is a helpful increase in attention, a focusing of mental, physical, sensory, and emotional systems toward analyzing the environment for seriousness of threat to oneself and mobilizing the most appropriate response. The efficiency with which humans can activate this sensory and mental system is great and assists in many life-saving decisions. When a person is in such a state, however, he or she cannot do a lot of other things simultaneously. This dedication to self-preservation helps to explain how pathologic anxiety states can override other functions and render the individual dysfunctional. Similarly, shutting down of responsiveness to the outside environment may be self-preservative. This is a normal response to extreme fatigue, shock after injury, or sudden and abrupt loss. When the state persists or develops without a specific trigger, it may decrease the
From the Departments of Psychiatry and Neurology, University of New Mexico Health Sciences Center and School of Medicine, Albuquerque, New Mexico
MEDICAL CLINICS OF NORTH AMERICA VOLUME 84 * NUMBER 4 * JULY 2000
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individual’s ability to think, respond, or enjoy usual activities. Pathologic depressive states can make a person’s physiology change such that all experiences are altered, impinging on important developmental achievements. It is important to assist adolescents to develop healthy and flexible responses to different stressors. Recognizing anxiety and depression responses that are healthy and differentiating them from disorders that need more aggressive treatment is critical support for adolescents’ health development. ANXIETY RESPONSES Performance, Acceptance, and Sexual Interest
Many activities involving social performance affect adolescents. Although they may seem to like the attention they garner, often the crowdseeking behavior of adolescents is a means of maintaining anonymity and reducing their own sense of vulnerability. Performance anxieties may range from bashfulness in front of new individuals to phobias arising from focused awareness of minor physical abnormalities (see other articles). Acceptance by the peer group in addition to the fundamental acceptance from parents is a crucial aspect to development and well-being. A great deal of energy and effort may be directed at making sure that they are fitting in as seamlessly as possible with their peers. From within the peer group or from outside interests, special personal relationships start to emerge that have sexual feelings associated with them. It is natural that fears about being able to perform sexual acts normally and well become a major concern. The physical changes occurring during adolescence promote the psychologic changes indirectly through sex hormone levels and directly through appearance and other visual cues. Insecurities about one’s (sexual) appeal to another may be masked by newly emergent obsessions with particulars of dress. Most people have time to adapt to these interests and pressures and develop a flexible repertoire of responses. Lack of flexibility is the hallmark of behavior that should draw the attention of the clinician. Pathophysiology of Anxiety
The limbic and basal ganglia systems are essential components to goal-setting and goal-attaining functions of the central nervous system. Things that are recognized and remembered as rewards must be differentiated from things that are experienced as undesirable. Activity can be directed toward the desired goals (initially the basic experiences of food, water, and sleep) but must be monitored and the feedback information incorporated into any action. In other words, information about the potential dangerousness must be integrated with the intended action; the amygdala must provide modulating information to the motor control
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systems so that meaningful actions can be taken.21The limbic structures and basal ganglia are in intimate communication with the sensorimotor cortex area and prefrontal cortex to execute anticipated and reactive responses to a changing environment. Gray19,2o has proposed a model involving the septohippocampal system and associated Papez circuit as performing a general comparator function, comparing actual and expected (predicted) states of the world. Anxiety reflects activity within a behavioral inhibition system. This activity is responding to threat of punishment, to omission of anticipated reward, and to perceived extreme novelty by inhibiting ongoing behavior and giving increased attention to environmental cues. This model includes neuroanatomic structures based on empiric evidence: Anxiolytic drugs have primary action on sites in the septohippocampal system; anxiety evoked by fear conditioning involves the amygdala; fight-or-flight behavior involves the amygdala, medial hypothalamus, and central gray area. The formation of cue-reinforcement associations (fear conditioning) takes place in the amygdala and are transferred by way of the entorhinal cortex to the hippocampus. Effect of past and current motor programs is relayed from the prefrontal cortex by way of the entorhinal connection to the hippocampus. Ascending noradrenergic and serotoninergic systems modulate the input and relative gain in this system. Output from the hippocampus through the cingulate cortex or through the nucleus accumbens can interrupt motor behaviors and complex automatic behaviors. Symptoms of anxiety may be organized into three general categories: autonomic, behavioral, and cognitive. The model outlined previously provides a parsimonious explanation of a mechanism by which arousal symptoms and avoidant behavior can assume progressively intrusive roles in a person’s life. Similarly, words can amplify the activity in these circuits, bringing new meaning and impact from frontal and prefrontal areas with stored experiences and becoming as effective as danger at activating these interrelated systems. Roy-Byrne et a147found that peripheral markers of autonomic regulation did not differ in patients with panic disorder, obsessive-compulsive disorder, or anxiety disorder or normal controls. The attribution of meaning to physiologic symptoms and the likelihood of having physiologic symptoms are not due to an abnormal peripheral nervous system regulatory system. Diagnostic Considerations The disorders of anxiety are grouped in the accompanying box according to the DSM-IV.2The most prevalent are the simple and social phobias (11%to 13%),but generalized anxiety disorder (GAD), present in about 5% of the general population, causes more pervasive disruption of functioning. Persistent and disabling symptoms of anxiety may be accompanied by acute panic attacks, which entail abrupt feelings of
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suffocation, impending doom, distortion of the perception of time, and even the sense that one is dying. Most individuals who experience these acute attacks are not aware of the psychologic stressor that precipitated the first attack or recurrences. With time, increases of physical symptoms, such as the pulse rate, may trigger either panic or anxiety responses. In other words, the body tends to habituate the arousal response, rather than to habituate to the arousal.
Diagnostic Categories of Anxiety Disorders
Generalized anxiefy disorder: uncontrollable, excessive anxiety for more days than not, for at least a 6-month period Panic disorder: intense escalating fear accompanied by at least 4 of 13 somatic and cognitive symptoms: may feel like having a heart attack: with or without agoraphobia Agoraphobia: pervasive avoidance of certain situations that bring on excessive anxiety or panic Specific phobia: persistent fear of exposure to possible scrutiny by others: the avoidant behavior interferes with functioning at work or in social situations, and the person is markedly distressed about the problem Obsessive-compulsive disorder: recurrent, distressful obsessions (thoughts) or compulsions (behaviors) that significantly interfere with social, academic, and daily function; resisting the obsession or compulsion causes anxiety to escalate rapidly to intolerable levels Post-traumatic stress disorder: onset some time after traumatic event; experience produced intense fear, helplessness, or horror: person experiences flashbacks, recurrent and intrusive recollections of the event, feelings of detachment, guilt, sleep problems, and many anxious and somatic symptoms of arousal Acute stress disorder: similar to posttraumatic stress disorder but limited to 2 days to 4 weeks Anxiety disorder due to general medical condition: symptoms of anxiety, obsessive-compulsive disorder, or panic that are directly linked to a medical condition; often atypical for age of onset, course, or family history Substance-inducedanxiety disorder: anxiety symptoms (may not meet full criteria of above-listed disorders) due to direct exposure to drug of abuse, medication, or exposure to a toxin
Prevalence of anxiety or depression in the general population of teenagers is not well characterized. Kramer and Garralda30 interviewed adolescents and their parents in a general practitioner setting in the United Kingdom. They found that physicians diagnosed the most severe disorders accurately; however, many children (ages 13 to 16 years) presented with physical complaints rather than with psychologic or psychiatric distress. Anxiety and depressive disorders were correlated with complaints of more than one physical disorder. An earlier study of
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adults in primary care settings in the United States reported direct correlation between anxiety or depressive disorder and increased numIndividuals with zero to one physical probber of physical lem had an incidence of 1% of anxiety disorder, whereas individuals with more than nine physical symptoms had an incidence of 48% of anxiety disorder; similarly, 1.5% and 60% respectively met criteria for depression. Although the overlap of having both diagnoses was high, it was not complete. Lecrubier and U s t ~ found n ~ ~ the prevalence of psychiatric disorders was 28% in 14 worldwide primary care settings. There was particularly high morbidity for individuals having both depression and panic disorder. The need for aggressive treatment of this dual diagnosis was underscored. The effect of locale on prevalence and severity of disorder is significant. McConaughy and A ~ h e n b a c hfound ~ ~ significant differences between university hospital outpatient clinic settings and school-based reports. The clinical settings were sampling children with more illness and more severe symptoms. Lynskey et a136reported on a cohort of children followed from birth to age 15 years. Children of parents with alcohol dependence (one or both) had 1.6 to 3 fold higher rates of psychiatric illnesses by midadolescence compared with matched controls. There was no difference in relative risk or in symptoms between boys and girls. Later adolescent girls (ages 15 to 18) may be at greater risk for anxiety and depression (17%)when there is higher maternal stress and greater marital strain in the Bardone et a14 found that anxiety disorder in girls aged 15 years was correlated with greater number of medical problems at age 21. Anxiety co-occurs with depression, conduct disorder, and attentiondeficit disorder in children ages 9 to 16 years old.6 Frequently, questions are asked about whether anxiety disorders are merely a worsening of a character trait. Biederman et a15 reviewed longer outcomes of children with and without behavioral inhibition. Those with introverted behavior had higher rates of anxiety disorders in later adolescence and early adulthood, which could lead to speculation about devising strategies that would reduce the likelihood of developing the clinical disorders. A different way to test the predilection to develop anxiety was used by Eke and M~Na1ly.l~ Challenging college students with carbon dioxide, they found that psychologic attention to physical symptoms was the best predictor of an anxious response, independent of sensitivity to carbon dioxide or personality style. These two studies remind clinicians not to depend too heavily on any single tool or examination in the diagnosis of anxious symptoms in adolescents; ignoring symptoms, however, invites more severe and long-term consequences to develop. Panic symptoms and panic disorder may present in adolescents with similar physiology and behavior as in adults or may have unique behavioral mannerisms (such as separation anxiety) that are retained from earlier childhood.40The author's careful review failed to show a persistent link of panic symptoms in childhood with panic disorder in adulthood.
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Treatment Strategies
GAD is an easily treated disorder. It is important to minimize the longer-lasting social and cognitive effects of severe anxiety by instituting treatment early. Medications can ameliorate or eradicate symptoms; however, they are more effective at preventing recurrence when combined with cognitive behavioral techniques. Cognitive and behavioral treatments are an important aspect of diminishing the intrusive systems of anxiety. Rethinking consequences, directing attention to realistic outcomes (as opposed to imagined disasters), and distracting focused attention are all components of thought-altering methods. Changes in behavioral routines that reflect these changes in thoughts or induced the changes are complementary. Rudd and Joiner48provide a primer on behavioral approaches to reducing anxiety and panic symptoms. Cognitive attribution is an important part of maintaining the disorders of anxiety and depression. Scott and 0 H a ~ found a ~ ~ that college-aged students with anxiety, depression, or mixed anxiety and depression had greater discrepancies in self-reported deficits between actual and idealized (what they thought they ought to be doing) actions. Medications can particularly relieve the physical manifestations of autonomic arousal and assist in diminishing the sensory stimulation that triggers exacerbation of anxiety. Antianxiety agents include tricyclic antidepressants, benzodiazepines, and bupropion (Table 1). Often the arousal systems of anxiety also disturb sleep patterns. Sedative-hypnotics are not generally beneficial as long-term treatment but may be Table 1. ANTIANXIETY MEDICATIONS Dose Day Drug Class
Drug Name
Comments
Benzodiazepines Lorazepam 2-10 Alprazolam 0.5-6 Diazepam 5-60 Clonazepam 14 Antipsychotics Thioridazine (Mellaril) 12.5-125
SSRIs
Buspirone P-Blocker
Olanzapine
5-10
Paroxetine
10-40
Fluoxetine
1040
Sertraline Fluvoxamine Venlafaxine Buspirone Propranolol
25-200 25-200 37.5-300 15-60 60-240
Half-life 12-18 h Half-life 6 1 4 h Half-life 20-36 h Half-life 3 0 4 0 h Risk of tardive dyskinesia is lowest of typical antipsychotics Atypical; monitor white blood cells Effective at anxiety and depression reduction Restlessness may exacerbate anxiety May sedate Give balance of dose in EM. FDA approved for GAD May be used alone or as add-on >60 mg, no increase in orthostatic hypotensive side effects
SSRI = Selective serotonin-reuptake inhibitors; FDA = US. Food and Drug Administration; GAD = generalized anxiety disorder.
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indicated for briefer (2 to 4 weeks) duration during crisis situations. The tricyclics are sedating (good as a sleeping aid as well), effective for the treatment of panic symptoms, and nonaddicting. They cause dry mouth, constipation, blurry vision (anticholinergic symptoms), and sometimes slowness of thinking process. In high or overdose amounts, the prolongation of cardiac conduction is a serious health risk. For this reason, it is advisable, even in teenagers, to obtain a baseline electrocardiogram to evaluate for toxic actions of the drug during therapy. Although benzodiazepines are one of the safest psychotropic medications, they can be dangerous when used by inattentive persons. Intoxication can occur because of their seemingly benign effects. People take more, without realizing how the dose is increasing and not anticipating the effect of half-life. Ataxia, slurred speech, disinhibition, and inattentiveness are early symptoms of too high a dose. In overdose situations, respiratory depression is life-threatening. Seizures are a complication of abrupt withdrawal or decrease in dosage. In combination with alcohol, the actions and side effects of benzodiazepines are potentiated. All persons should be advised not to drive when consuming alcohol with benzodiazepines and some when titrating dosages as well. den Boer et al" reviewed treatment of anxiety syndromes. Fluvoxamine showed that selective serotonin-reuptake inhibitors (SSRIs) are effective in reduction of anxiety components in social phobic, depressive, and panic disorders, whereas drugs that increase noradrenaline or block postsynaptic serotonin receptors do not produce the same reduction in anxiety. The side effects of SSRIs include sexual dysfunction and may be severe enough to warrant terminating treatment or attempting to decrease the dosage and add in symptom-reducing agents.33 Antipsychotic medications are also used to treat anxiety sympt o m ~ .A ' ~thorough risk-benefit analysis has not been conducted comparing antipsychotics and benzodiazepines. In general, the risk of physiologic dependence on benzodiazepines is perceived as less burdensome than the risk of developing involuntary movement disorder (tardive dyskinesia). Benzodiazepine withdrawal can be complicated. Patients with panic disorder are reported to have extreme difficulty discontinuing treatment. Klein et alZ9used carbamazepine (Tegretol) to mitigate the severity of withdrawal symptoms while discontinuing alprazolam (Xanax).In their double-blind (carbamazepine-placebo) study, this use assisted the patients with panic disorder but made little difference to those with GAD. All of the patients with panic disorder who received placebo were not able to complete the 4-week withdrawal phase and dropped out of the study. DEPRESSEDRESPONSES
Biologic Basis The noradrenergic theory of mood disorders was proposed in the 1960s.*,50 Mania was hypothesized as due to excess monoamines and
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depression resulting from an absence or relative lack of catecholamines, particularly noradrenaline. Projections of noradrenergic neurons extend from midline midbrain structures throughout subcortical and cortical areas, including cortex, limbic areas, thalamus, hypothalamus, cerebellum, sensory nuclei, and down into the spinal cord. Drugs that stimulate noradrenergic activity are not uniformly successful antidepressants. The serotoninergic theory proposes that a deficit of serotonin (in central nervous system) causes the onset of depressive mood.1o,43 Increased serotonin availability (e.g., by reuptake inhibition) alleviates symptoms, including decreased energy, sadness, impaired concentration, disrupted sleep, and poor self-image. In some theorists’ view, these neurotransmitter systems, which have closely overlapping circuits and receptor distributions, always are acting in concert with each other. In the early 1970s, cholinergic mechanismsz5and dopaminergic mechanismsMfor onset of depression were presented. It has been reported that cholinomimetic properties increase depressed mood and anergic response, especially in persons prone to depressions or with family history of depression. Dopamine metabolites are lower than normal in many patients showing psychomotor retardation and severe suicidal ideation, features of rnelancholic depression. Levels of noradrenaline have been reported increased and more variable in persons with melancholic-psychotic depression than in cont r o l ~Peripheral .~~ markers of presynaptic a-adrenergic, postsynaptic padrenergic, and 3H-imipramine receptors do not correlate well with mood states, and they do not predict groups of patients’ responses to drugs directed at these receptors. There are many studies of abnormalities of neuroendocrinologic changes in depression. This research has been prompted by knowledge of hypothalamic peptides that are regulated by monoamines affecting mood states, with widespread receptor distribution throughout the limbic system, in turn, controlling hypothalamic activity. Approximately half of patients with melancholic depression show depressed cortisol suppression to the dexamethasone test; in other words, they maintain an aberrantly raised level of cortisol during the day instead of a diurnal variation. To date, measures of hypothalamic-hypophysial-adrenal axis function do not predict response to treatment or longer-term outcomes.
Diagnosis The differential diagnosis of depressive disorders (see accompanying box) is complicated by personality characteristics and duration of symptoms. Criteria for major depression require that symptoms have lasted for more than 2 weeks. These include vegetative symptoms of sleep and appetite disturbance in addition to disturbance of mood and sensations of worthlessness and helplessness. The diagnosis of dysthymia is challenging because of being less pronounced in severity and lasting for months or years. Depression may be superimposed on dys-
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thymia or bipolar illness. Substance use, such as recurrent alcohol abuse or acute intoxication, may induce dangerous and impulsive self-destructive behavior with depressed feelings. In some cases, the substance use is a poor attempt to treat an underlying dysphoria. That is, it is a poor attempt because alcohol is a central nervous system depressant.
Diagnostic Categories of Depressive Disorders
Major depressive disorder: symptoms of depressed mood, disturbance in sleep, decreased concentration and attention, change in appetite and weight, anhedonia and anergia, feelings of helplessness and hopelessness, with or without suicidal ideation or intent must have been present for at least 2 weeks in the absence of another medical or psychiatric condition; may occur as discrete episode or recurrent episodes Dysthymia: persistent and pervasive feelings of sadness that are not as severe as major depressive disorder; tend to respond to similar treatments Bipolar disorder: characterized by distinct periods of depression and mania; may exhibit primarily depressed, manic, or mixed patterns; manic periods usually of shorter duration, with decreased sleep, increased energy, grandiose ideation, rapid thoughts and speech, irritability or hostility, impulsive expansive behavior in poor judgment (e.g., spending money the person does not have) Cyclothymia: less severe form of fluctuation between manic and depressed mood states; may occur in rapid succession to each other Mood disorder due to medical condition: depression can be directly traced to medical condition or treatment Substance-related mood disorder: depressed mood is induced by physiologic effects of direct ingestion of drug of abuse, medication, or exposure to a toxin
In general, females show increased rates for depressive responses beginning in middle school. Genetic and environmental factors appear to have a stronger influence on females throughout adolescence in the 51 Adolescents with development of depressive and anxious responses.24* depression and conduct disorder reported more limited social interactions and higher dissatisfaction than matched They reported negative views of their family climate. Having severe symptoms of depression as an adolescent predicted a two to three fold increased risk of having at least one major depressive episode in adult life, according to Pine et al.42 Personality traits of negative affect and anxiety may predispose 26 Coping styles may ameliorate tendencies to females to depre~sion.~, depression and may be sensitive to treatment in college students according to Hagerty and Williams.22In males with conduct problems and depressive symptoms, neither was predictive of overall outcome but
together resulted in problem outcomes in multiple areas of fun~tioning.~ Depression in adolescent girls was found to predict higher rates of marriage at a younger age and greater marital dissatisfaction.ls K W O ~ ~ ~ examined cognitive and psychodynamic influences on level of dysphoria in undergraduate college students. This study supported that hopelessness was reinforced by attributing control outside of one's self and turning against self. An analysis of morbidity resulting from anxiety and depression was reported by Allgulander.' Allgulander reviewed records in Sweden from 1973 through 1983 and found increased death rate (across the life span) in persons who had recently been hospitalized and had medical problems, with anxiety, depressive neurosis, or both. Although depression was associated with twice the risk of suicide as that of anxiety, both were substantial contributors to self-inflicted death in people from the ages of adolescence to 45 years. Lower socioeconomic status and lower levels of education were correlated with depression, obesity, and attempted suicide in adolesc e n t ~Additionally, .~~ depression may be expected as a secondary condition to other medical conditions, such as epilepsy. Dunn et all2 reported depression in 23% of adolescent patients with epilepsy. Case reports of depression in specific syndromes, such as Kleine-Levin syndr0me,3~remind the clinician of the presence of psychopathology in genetic disorders of metabolism and neurologic function. At least one study has found that depressive symptoms (including depressive disorder) are associated with smoking (cigarettes) in teenager^.'^ Treatment issues
Treatment strategies should be flexible and consistent with the individual's and family's belief systems. Supportive counseling or psychotherapy is indicated for stress reactions, brief reactive adjustment disorders, and adaptation to chronic disorders. Renaud et a146found that adolescents who responded to supportive and intensive psychotherapeutic measures had better outcomes and that a positive response could assist in determination of who should receive medication treatment for depression. Depressive symptoms may resolve with psychotherapy. Repetitive thinking and behaviors that lead to recurrent depressive or anxious thought patterns must be addressed to permit long-term healthy outcomes, beyond the acute treatment response. Cognitive behavior therapy is an effective and structured treatment approach to change habitual thinking and behavior.45 Psychotherapy techniques usually focus on the interpersonal meanings and interactions people engage in. Changes generally occur more slowly with these techniques than with medications but may be more fundamental in terms of increased personal awareness of factors that increase the person's well-being and selfaffirmation and that decrease tendencies toward self-deprecation and
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RECOGNIZING AND TREATING ANXIETY AND DEPRESSION IN ADOLESCENTS
self-blame. Often the physiologic arousal is interrupting attempts at verbalizing internal feeling states. Especially in these cases, pharmacologic treatment must be initiated for psychologic work to begin and to proceed. Medications for the treatment of depressive symptoms, with or without anxiety, are geared toward increasing serotoninergic activity or the noradrenergic system (Table 2). SSRIs are perhaps most easily tolerated. Although fluoxetine (Prozac) has been reported to contribute to suicide in early studies, it appears that the induction of restlessness (akathisia) unexpected and untreated is the cause of this driven behavior. All SSRIs may cause an awakening or sedating response, and the timing of ingestion should be arranged depending on the individual's response. SSRIs have a generally low rate of side effects, but the ones more frequently seen include prolongation of time to sexual climax; anorgasmia; gastric distress, with nausea, intestinal gas, or diarrhea; headaches; and weight gain or loss. Tricyclic antidepressants are effective agents for mixed anxiety and depression disorders and depression with prominent sleep disturbance and for people who are unable to tolerate SSRI side effects. Tricyclic antidepressants affect cardiac conduction and may cause profound orthostatic hypotension. A baseline electrocardiogram should be obtained to screen for subtle changes in cardiac conduction. Monoamine oxidase inhibitors are indicated in the treatment of atypical depression but must be used even more cautiously in adolescents than adults because of the need to monitor dietary restrictions (high tyramine containing foods may precipitate a hypertensive crisis). Adolescent women with reproductive capability should be counseled about the potential teratogenic effects of all medications, including tricyclic antidepressants. Concomitant substance abuse must be addressed simultaneously and the treatment efforts integrated with each other. Several studies Table 2. ANTIDEPRESSANT MEDICATIONS Drug Class
SSRI
Drug Name
Sertraline (Zoloft)
Dose (mg/d) 12.5-200
Paroxetine (Paxil) 10-50 Fluoxetine (Prozac) 10-60 Venlafaxine (Effexor) 37.5-375 Fluvoxamine (Luvox) 25-200 25-250 TCA Amitriptyline (Elavil) 25-250 Imipramine (Tofranil) Desipramine (Norpramin) 25-250 20-200 Nortriptyline (Pamelor) MA01 Phenelzine (Nardil) 15-45 Tranylcypromine (Parnate) 10-30
Comments Sedation, early in treatment; weight gain frequent Decreases anxiety Effective in bulimia; activating Little sedation Decreases obsessive-compulsive behavior Used in pain Decreases anxiety Metabolite of imipramine Alerting
SSRI = Selective serotonin-reuptakeinhibitor; TCA amine oxidase inhibitor.
=
tricyclic antidepressant; MA01
=
mono-
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have shown that substance abuse correlated with poor compliance after hospitalization and with low level of family s ~ p p o r t .23,~ ,35 At a minimum, these factors must raise the attention of the treatment teams.52 DETERMINING ACUITY AND IMPULSIVITY
Responsibility for determining the severity of symptoms lies with the examining professional. This responsibility includes assessment of suicidal intent and likelihood of attempting suicide. Factors that must be included in such an assessment are (1) imminent danger to self or others, awareness of danger, plans and access to means, and acute stressors; (2) social network and meaningfulness of connections and capacity for intimacy; (3) substance abuse or dependence-current intoxicated state, and likelihood of access to intoxicating drugs in immediate future; and (4)documentation of concerns, communications, and recommendations. The presence of reliable and supportive adults who can participate in providing means of access to treatment and preventing impulsive self-destructive acts are critical for outpatient management of unstable patients. Practitioners should not feel hesitant to request a second opinion from a trained colleague. Determination of suicidal risk can be murky, and the consequences of impulsive, rash acts are serious. Collaborative decision making is the best means of preventing unnecessary accident and death. SUMMARY
Recognition of depressive and anxiety disorders in adolescents reduces morbidity, mortality, and lifetime risk for psychiatric illness and maladaptive behaviors. Effective treatments for these disorders are available and are associated with minimal severe side effects. Because adolescents tend to underreport their psychologic distress, screening for these disorders in the primary care setting is incumbent on the Depression or anxiety may be a primary or a secondary condition-with each other and with other medical illness. Substance abuse, including cigarettes, should not be overlooked as an accompanying risk factor for poor health care habits and as an indicator of degree of family (lack of) support. Adolescents at risk should be screened and their symptoms taken seriously. This brief overview does not focus on the need for primary care clinicians to seek assistance and support of psychiatrists in the diagnosis and development of treatment algorithms. All clinicians should be reminded that judgments about peoples’ internal mental states and function are difficult to assess objectively and with compassion. Initial assessment in the primary care setting should include a telephone consultation with a reliable psychiatric colleague and referral for more in-depth evaluation in the event of more complicated course. These disorders
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need to be treated comprehensively because of the lifelong implications that having a chronic disease bear on the individual and his or her physiology. Primary care clinicians are pivotal instruments in engaging adolescents to embrace appropriate therapeutic measures for their current and future health.
References 1. Allgulander C: Suicide and mortality patterns in anxiety neurosis and depressive neurosis. Arch Gen Psychiatry 51:708-712, 1994 2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4 (DMS-IV). Washington, DC, American Psychiatric Association Press, 1994 3. Aseltine RH Jr, Gore S, Colten ME: The co-occurrence of depression and substance abuse in late adolescence. Dev Psychopathol 10:549-570, 1998 4. Bardone AM, Moffitt TE, Caspi A, et al: Adult physical health outcomes of adolescent girls with conduct disorder, depression, and anxiety. J Am Acad Child Adolesc Psychiatry 37594601, 1998 5. Biederman J, Rosenbaum JF, Bolduc-Murphy EA, et al: A 3-year follow-up of children with and without behavioral inhibition. J Am Acad Child Adolesc Psychiatry 323814821, 1993 6. Bird HR, Gould MS, Staghezza BM: Patterns of diagnostic comorbidity in a community sample of children aged 9 through 16 years. J Am Acad Child Adolesc Psychiatry 32361368, 1993 7. Bouhuys AL, Geerts E, Gordijn MC: Gender-specific mechanisms associated with outcome of depression: Perception of emotions, coping and interpersonal functioning. Psychiatry Res 85:247-261, 1999 8. Bunney WF Jr, Davis JB: Norepinephrine in depressive reactions: A review. Arch Gen Psychiatry 13:483-494, 1965 9. Capaldi DM, Stoolmiller M Co-occurrence of conduct problems and depressive symptoms in early adolescent boys: 111. Prediction to young-adult adjustment. Dev Psychopathol 11:59-84, 1999 10. Coppen AJ, Dougan DP: Serotonin and its place in the pathogenesis of depression. J Clin Psychiatry 49:4-11, 1988 11. den Boer JA, Westenberg HG, De Leeuw AS, et al: Biological dissection of anxiety disorders: The clinical role of selective serotonin reuptake inhibitors with particular reference to fluvoxamine. Int Clin Psychopharmacol 9:47-52, 1995 12. Dunn DW, Austin JK, Huster GA: Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry 38:1132-1138, 1999 13. Eke M, McNally RJ: Anxiety sensitivity, suffocation fear, trait anxiety, and breathholding duration as predictors of response to carbon dioxide challenge. Behav Res Ther 34:603-607, 1996 14. El-Khayat R, Baldwin D S htipsychotic drugs for non-psychotic patients: Assessment of the benefit / risk ratio in generalized anxiety disorder. J Psychopharmacol 12323329, 1998 15. Escobedo LG, Reddy M, Giovino GA: The relationship between depressive symptoms and cigarette smoking in US adolescents. Addiction 93:433-440, 1998 16. Goldberg C: Cognitive-behavioral therapy for panic: Effectiveness and limitations. Psychiatr Q 692344, 1998 17. Goodman E: The role of socioeconomic status gradients in explaining differences in US adolescents’ health. Am J Public Health 89:1522-1528, 1999 18. Gotlib IH, Lewinsohn PM, Seeley J R Consequences of depression during adolescence: Marital status and marital functioning in early adulthood. J Abnorm Psycho1 107:868890, 1998 19. Gray J A Drug effects on fear and frustration: Possible limbic site of action of minor
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tranquilizers. In Iverson LL, Iverson SD, Snyder SH (eds): Handbook of Psychopharmacology. New York, Plenum, 1977, pp 433-529 20. Gray JA: The Psychology of Fear and Stress, ed 2. Cambridge, Cambridge University Press, 1987 21. Gray JA: A model of the limbic system and basal ganglia: Applications to anxiety and schizophrenia. In Gazzaniga MS (ed): The Cognitive Neurosciences. Cambridge, MA, MIT Press, 1995, pp 1165-1176 22. Hagerty BM, Williams RA: The effects of sense of belonging, social support, conflict, and loneliness and depression. Nurs Res 48:215-219, 1999 23. Hoffman JP, Su S S Stressful life events and adolescent substance use and depression: Conditional and gender differentiated effects. Subst Use Misuse 33:2219-2262, 1998 24. Jacobson KC, Rowe DC: Genetic and environmental influences on the relationships between family connectedness, school connectedness and adolescent depressed mood: sex differences. Dev Psychol 35:926-939, 1999 25. Janowsky DS, El Yousef MK, Davis JM: A cholinergic-adrenergic hypothesis of depression and mania. Lancet 2:6732-6735, 1972 26. Joiner TE Jr, Blalock JA, Wagner KD: Preliminary examination of sex differences in depressive symptoms among adolescent psychiatric inpatients: The role of anxious symptoms and generalized negative affect. J Clin Child Psychol 28:211-219, 1999 27. Kelly CB, Cooper SJ: Differences and variability in plasma noradrenaline between depressive and anxiety disorders. J Psychopharmacol 12161-167, 1998 28. Kessler D, Lloyd K, Lewis G, et al: Cross sectional study of symptom attribution and recognition of depression and anxiety in primary care. BMJ 3B436-439, 1999 29. Klein E, Colin V, Stolk J, et al: Alprazolam withdrawal in patients with panic disorder and generalized anxiety disorder: Vulnerability and effect of carbamazepine. Am J Psychiatry 151:1760-1766, 1994 30. Kramer T, Garralda ME: Psychiatric disorders in adolescents in primary care. Br J Psychiatry 173:508-513, 1998 31. Kroenke K, Spitzer RL, Williams JB, et al: Physical symptoms in primary care: Predictors of psychiatric disorders and functional impairment. Arch Fam Med 33774-779, 1994 32. Kwon P: Attributional style and psychodynamic defense mechanisms: Towards an integrative model of depression. J Pers 67645-658, 1999 33. Labbate LA: Sex and serotonin reuptake inhibitor antidepressants. Psychiatr AM 29:571-579, 1999 34. Lecrubier Y, Ustun TB: Panic and depression: A worldwide primary care perspective. Int Clin Psychopharmacol 13:7-11, 1998 35. Lloyd A, Horan WK, Borgar SR, et al: Predictors of medication compliance after hospital discharge in adolescent psychiatric patients. J Child Adolesc Psychopharmacol 81133-141, 1998 36. Lynskey MT, Fergusson DM, Horwood LJ: The effect of parental alcohol problems on rates of adolescent psychiatric disorders. Addiction 89:1277-1286, 1994 37. McConaughy SH, Achenbach TM: Comorbidity of empirically based syndromes in matched general population and clinical samples. J Chilh Psychol Psychiatry 35:11411157, 1994 38. Monck E, Graham P, Richman N, et al: Adolescent girls: 11. Background factors in anxiety and depressive states. Br J Psychiatry 165:770-780, 1994 39. Mukaddes NM, Alyanak B, Kora ME, et al: The psychiatric symptomatology in KleineLevin syndrome. Child Psychiatry Hum Dev 29:253-258, 1999 40. Ollendick TH, Mattis SG, King NJ: Panic in children and adolescents: A review. J Child Psychol Psychiatry 35:113-134, 1994 41. Olsson GI, Nordstrom ML, Arinell H, et al: Adolescent depression: Social network and family climate-a case control study. J Child Psychol Psychiatry 40:227-237, 1999 42. Pine DS, Cohen E, Cohen P, et al: Adolescent depressive symptoms as predictors of adult depression: Moodiness or mood disorder? Am J Psychiatry 156:133-135, 1999 43. Prange AJ Jr, Wilson IC, Lynn CW: L-tryptophan in mania: Contribution to a permissive hypothesis of affective disorders. Arch Gen Psychiatry 30:5&62, 1974
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44. Radrup A, Munkvad I, Fog R Mania, Depression and Brain Dopamine: Current Developments in Psychopharmacology. New York, Spectrum, 1975 45. Reinecke MA, Ryan NE, DuBois DL: Cognitive-behavioral therapy of depression and depressive symptoms during adolescence: A review and meta-analysis. J Am Acad Child Adolesc Psychiatry 37:26-34, 1998 46. Renaud J, Brent DA, Baugher M, et al: Rapid response to psychosocial treatment for adolescent depression: A two-year follow-up. J Am Acad Child Adolesc Psychiatry 37:1184-1190, 1998 47. Roy-Byrne P, Cowley DS, Stein MB, et al: Cardiovascular and catecholamine response to orthostasis in panic and obsessive-compulsive disorder and normal controls: effects of anxiety and novelty. Depress Anxiety 6:159-164, 1997 48. Rudd MD, Joiner T The role of symptom induction in the treatment of panic and anxiety: Identifiable domains, conditional properties, and treatment targets. Behav Modif 22:9&107, 1998 49. Scott L, OHara MW: Self-discrepancies in clinically anxious and depressed university students. J Abnorm Psycho1 102:282-287, 1993 50. Schildkraut J: The catecholamine hypothesis of affective disorders: A review of supporting evidence. Am J Psychiatry 113:1407-1411, 1965 51. Schraedley PK, Gotlib IH, Hayward C: Gender differences in correlates of depressive symptoms in adolescents. J Adolesc Health 25:98-108, 1999 52. Zeitlin H: Psychiatric comorbidity with substance misuse in children and teenagers. Drug Alcohol Depend 55:225-234, 1999
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RECOGNIZING AND TREATING ANXIETY AND DEPRESSION IN ADOLESCENTS Normal and Abnormal Responses Alya Reeve, MD
The vicissitudes of adolescence often make an individual question his or her own sanity. Extremes of emotion are not uncommon; however, prolonged states of an emotional extreme and abrupt changes in patterns of usual behavior are indicators of abnormal processes. Anxiety is a normal physiologic and psychologic response to change in or around an individual. Signal anxiety occurs normally to alert the individual that there is something not right with the environment-that a potential danger exists. This arousing of the defense system, toward a fight-or-fight response, is a helpful increase in attention, a focusing of mental, physical, sensory, and emotional systems toward analyzing the environment for seriousness of threat to oneself and mobilizing the most appropriate response. The efficiency with which humans can activate this sensory and mental system is great and assists in many life-saving decisions. When a person is in such a state, however, he or she cannot do a lot of other things simultaneously. This dedication to self-preservation helps to explain how pathologic anxiety states can override other functions and render the individual dysfunctional. Similarly, shutting down of responsiveness to the outside environment may be self-preservative. This is a normal response to extreme fatigue, shock after injury, or sudden and abrupt loss. When the state persists or develops without a specific trigger, it may decrease the
From the Departments of Psychiatry and Neurology, University of New Mexico Health Sciences Center and School of Medicine, Albuquerque, New Mexico
MEDICAL CLINICS OF NORTH AMERICA VOLUME 84 * NUMBER 4 * JULY 2000
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individual’s ability to think, respond, or enjoy usual activities. Pathologic depressive states can make a person’s physiology change such that all experiences are altered, impinging on important developmental achievements. It is important to assist adolescents to develop healthy and flexible responses to different stressors. Recognizing anxiety and depression responses that are healthy and differentiating them from disorders that need more aggressive treatment is critical support for adolescents’ health development. ANXIETY RESPONSES Performance, Acceptance, and Sexual Interest
Many activities involving social performance affect adolescents. Although they may seem to like the attention they garner, often the crowdseeking behavior of adolescents is a means of maintaining anonymity and reducing their own sense of vulnerability. Performance anxieties may range from bashfulness in front of new individuals to phobias arising from focused awareness of minor physical abnormalities (see other articles). Acceptance by the peer group in addition to the fundamental acceptance from parents is a crucial aspect to development and well-being. A great deal of energy and effort may be directed at making sure that they are fitting in as seamlessly as possible with their peers. From within the peer group or from outside interests, special personal relationships start to emerge that have sexual feelings associated with them. It is natural that fears about being able to perform sexual acts normally and well become a major concern. The physical changes occurring during adolescence promote the psychologic changes indirectly through sex hormone levels and directly through appearance and other visual cues. Insecurities about one’s (sexual) appeal to another may be masked by newly emergent obsessions with particulars of dress. Most people have time to adapt to these interests and pressures and develop a flexible repertoire of responses. Lack of flexibility is the hallmark of behavior that should draw the attention of the clinician. Pathophysiology of Anxiety
The limbic and basal ganglia systems are essential components to goal-setting and goal-attaining functions of the central nervous system. Things that are recognized and remembered as rewards must be differentiated from things that are experienced as undesirable. Activity can be directed toward the desired goals (initially the basic experiences of food, water, and sleep) but must be monitored and the feedback information incorporated into any action. In other words, information about the potential dangerousness must be integrated with the intended action; the amygdala must provide modulating information to the motor control
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systems so that meaningful actions can be taken.21The limbic structures and basal ganglia are in intimate communication with the sensorimotor cortex area and prefrontal cortex to execute anticipated and reactive responses to a changing environment. Gray19,2o has proposed a model involving the septohippocampal system and associated Papez circuit as performing a general comparator function, comparing actual and expected (predicted) states of the world. Anxiety reflects activity within a behavioral inhibition system. This activity is responding to threat of punishment, to omission of anticipated reward, and to perceived extreme novelty by inhibiting ongoing behavior and giving increased attention to environmental cues. This model includes neuroanatomic structures based on empiric evidence: Anxiolytic drugs have primary action on sites in the septohippocampal system; anxiety evoked by fear conditioning involves the amygdala; fight-or-flight behavior involves the amygdala, medial hypothalamus, and central gray area. The formation of cue-reinforcement associations (fear conditioning) takes place in the amygdala and are transferred by way of the entorhinal cortex to the hippocampus. Effect of past and current motor programs is relayed from the prefrontal cortex by way of the entorhinal connection to the hippocampus. Ascending noradrenergic and serotoninergic systems modulate the input and relative gain in this system. Output from the hippocampus through the cingulate cortex or through the nucleus accumbens can interrupt motor behaviors and complex automatic behaviors. Symptoms of anxiety may be organized into three general categories: autonomic, behavioral, and cognitive. The model outlined previously provides a parsimonious explanation of a mechanism by which arousal symptoms and avoidant behavior can assume progressively intrusive roles in a person’s life. Similarly, words can amplify the activity in these circuits, bringing new meaning and impact from frontal and prefrontal areas with stored experiences and becoming as effective as danger at activating these interrelated systems. Roy-Byrne et a147found that peripheral markers of autonomic regulation did not differ in patients with panic disorder, obsessive-compulsive disorder, or anxiety disorder or normal controls. The attribution of meaning to physiologic symptoms and the likelihood of having physiologic symptoms are not due to an abnormal peripheral nervous system regulatory system. Diagnostic Considerations The disorders of anxiety are grouped in the accompanying box according to the DSM-IV.2The most prevalent are the simple and social phobias (11%to 13%),but generalized anxiety disorder (GAD), present in about 5% of the general population, causes more pervasive disruption of functioning. Persistent and disabling symptoms of anxiety may be accompanied by acute panic attacks, which entail abrupt feelings of
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suffocation, impending doom, distortion of the perception of time, and even the sense that one is dying. Most individuals who experience these acute attacks are not aware of the psychologic stressor that precipitated the first attack or recurrences. With time, increases of physical symptoms, such as the pulse rate, may trigger either panic or anxiety responses. In other words, the body tends to habituate the arousal response, rather than to habituate to the arousal.
Diagnostic Categories of Anxiety Disorders
Generalized anxiefy disorder: uncontrollable, excessive anxiety for more days than not, for at least a 6-month period Panic disorder: intense escalating fear accompanied by at least 4 of 13 somatic and cognitive symptoms: may feel like having a heart attack: with or without agoraphobia Agoraphobia: pervasive avoidance of certain situations that bring on excessive anxiety or panic Specific phobia: persistent fear of exposure to possible scrutiny by others: the avoidant behavior interferes with functioning at work or in social situations, and the person is markedly distressed about the problem Obsessive-compulsive disorder: recurrent, distressful obsessions (thoughts) or compulsions (behaviors) that significantly interfere with social, academic, and daily function; resisting the obsession or compulsion causes anxiety to escalate rapidly to intolerable levels Post-traumatic stress disorder: onset some time after traumatic event; experience produced intense fear, helplessness, or horror: person experiences flashbacks, recurrent and intrusive recollections of the event, feelings of detachment, guilt, sleep problems, and many anxious and somatic symptoms of arousal Acute stress disorder: similar to posttraumatic stress disorder but limited to 2 days to 4 weeks Anxiety disorder due to general medical condition: symptoms of anxiety, obsessive-compulsive disorder, or panic that are directly linked to a medical condition; often atypical for age of onset, course, or family history Substance-inducedanxiety disorder: anxiety symptoms (may not meet full criteria of above-listed disorders) due to direct exposure to drug of abuse, medication, or exposure to a toxin
Prevalence of anxiety or depression in the general population of teenagers is not well characterized. Kramer and Garralda30 interviewed adolescents and their parents in a general practitioner setting in the United Kingdom. They found that physicians diagnosed the most severe disorders accurately; however, many children (ages 13 to 16 years) presented with physical complaints rather than with psychologic or psychiatric distress. Anxiety and depressive disorders were correlated with complaints of more than one physical disorder. An earlier study of
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adults in primary care settings in the United States reported direct correlation between anxiety or depressive disorder and increased numIndividuals with zero to one physical probber of physical lem had an incidence of 1% of anxiety disorder, whereas individuals with more than nine physical symptoms had an incidence of 48% of anxiety disorder; similarly, 1.5% and 60% respectively met criteria for depression. Although the overlap of having both diagnoses was high, it was not complete. Lecrubier and U s t ~ found n ~ ~ the prevalence of psychiatric disorders was 28% in 14 worldwide primary care settings. There was particularly high morbidity for individuals having both depression and panic disorder. The need for aggressive treatment of this dual diagnosis was underscored. The effect of locale on prevalence and severity of disorder is significant. McConaughy and A ~ h e n b a c hfound ~ ~ significant differences between university hospital outpatient clinic settings and school-based reports. The clinical settings were sampling children with more illness and more severe symptoms. Lynskey et a136reported on a cohort of children followed from birth to age 15 years. Children of parents with alcohol dependence (one or both) had 1.6 to 3 fold higher rates of psychiatric illnesses by midadolescence compared with matched controls. There was no difference in relative risk or in symptoms between boys and girls. Later adolescent girls (ages 15 to 18) may be at greater risk for anxiety and depression (17%)when there is higher maternal stress and greater marital strain in the Bardone et a14 found that anxiety disorder in girls aged 15 years was correlated with greater number of medical problems at age 21. Anxiety co-occurs with depression, conduct disorder, and attentiondeficit disorder in children ages 9 to 16 years old.6 Frequently, questions are asked about whether anxiety disorders are merely a worsening of a character trait. Biederman et a15 reviewed longer outcomes of children with and without behavioral inhibition. Those with introverted behavior had higher rates of anxiety disorders in later adolescence and early adulthood, which could lead to speculation about devising strategies that would reduce the likelihood of developing the clinical disorders. A different way to test the predilection to develop anxiety was used by Eke and M~Na1ly.l~ Challenging college students with carbon dioxide, they found that psychologic attention to physical symptoms was the best predictor of an anxious response, independent of sensitivity to carbon dioxide or personality style. These two studies remind clinicians not to depend too heavily on any single tool or examination in the diagnosis of anxious symptoms in adolescents; ignoring symptoms, however, invites more severe and long-term consequences to develop. Panic symptoms and panic disorder may present in adolescents with similar physiology and behavior as in adults or may have unique behavioral mannerisms (such as separation anxiety) that are retained from earlier childhood.40The author's careful review failed to show a persistent link of panic symptoms in childhood with panic disorder in adulthood.
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Treatment Strategies
GAD is an easily treated disorder. It is important to minimize the longer-lasting social and cognitive effects of severe anxiety by instituting treatment early. Medications can ameliorate or eradicate symptoms; however, they are more effective at preventing recurrence when combined with cognitive behavioral techniques. Cognitive and behavioral treatments are an important aspect of diminishing the intrusive systems of anxiety. Rethinking consequences, directing attention to realistic outcomes (as opposed to imagined disasters), and distracting focused attention are all components of thought-altering methods. Changes in behavioral routines that reflect these changes in thoughts or induced the changes are complementary. Rudd and Joiner48provide a primer on behavioral approaches to reducing anxiety and panic symptoms. Cognitive attribution is an important part of maintaining the disorders of anxiety and depression. Scott and 0 H a ~ found a ~ ~ that college-aged students with anxiety, depression, or mixed anxiety and depression had greater discrepancies in self-reported deficits between actual and idealized (what they thought they ought to be doing) actions. Medications can particularly relieve the physical manifestations of autonomic arousal and assist in diminishing the sensory stimulation that triggers exacerbation of anxiety. Antianxiety agents include tricyclic antidepressants, benzodiazepines, and bupropion (Table 1). Often the arousal systems of anxiety also disturb sleep patterns. Sedative-hypnotics are not generally beneficial as long-term treatment but may be Table 1. ANTIANXIETY MEDICATIONS Dose Day Drug Class
Drug Name
Comments
Benzodiazepines Lorazepam 2-10 Alprazolam 0.5-6 Diazepam 5-60 Clonazepam 14 Antipsychotics Thioridazine (Mellaril) 12.5-125
SSRIs
Buspirone P-Blocker
Olanzapine
5-10
Paroxetine
10-40
Fluoxetine
1040
Sertraline Fluvoxamine Venlafaxine Buspirone Propranolol
25-200 25-200 37.5-300 15-60 60-240
Half-life 12-18 h Half-life 6 1 4 h Half-life 20-36 h Half-life 3 0 4 0 h Risk of tardive dyskinesia is lowest of typical antipsychotics Atypical; monitor white blood cells Effective at anxiety and depression reduction Restlessness may exacerbate anxiety May sedate Give balance of dose in EM. FDA approved for GAD May be used alone or as add-on >60 mg, no increase in orthostatic hypotensive side effects
SSRI = Selective serotonin-reuptake inhibitors; FDA = US. Food and Drug Administration; GAD = generalized anxiety disorder.
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indicated for briefer (2 to 4 weeks) duration during crisis situations. The tricyclics are sedating (good as a sleeping aid as well), effective for the treatment of panic symptoms, and nonaddicting. They cause dry mouth, constipation, blurry vision (anticholinergic symptoms), and sometimes slowness of thinking process. In high or overdose amounts, the prolongation of cardiac conduction is a serious health risk. For this reason, it is advisable, even in teenagers, to obtain a baseline electrocardiogram to evaluate for toxic actions of the drug during therapy. Although benzodiazepines are one of the safest psychotropic medications, they can be dangerous when used by inattentive persons. Intoxication can occur because of their seemingly benign effects. People take more, without realizing how the dose is increasing and not anticipating the effect of half-life. Ataxia, slurred speech, disinhibition, and inattentiveness are early symptoms of too high a dose. In overdose situations, respiratory depression is life-threatening. Seizures are a complication of abrupt withdrawal or decrease in dosage. In combination with alcohol, the actions and side effects of benzodiazepines are potentiated. All persons should be advised not to drive when consuming alcohol with benzodiazepines and some when titrating dosages as well. den Boer et al" reviewed treatment of anxiety syndromes. Fluvoxamine showed that selective serotonin-reuptake inhibitors (SSRIs) are effective in reduction of anxiety components in social phobic, depressive, and panic disorders, whereas drugs that increase noradrenaline or block postsynaptic serotonin receptors do not produce the same reduction in anxiety. The side effects of SSRIs include sexual dysfunction and may be severe enough to warrant terminating treatment or attempting to decrease the dosage and add in symptom-reducing agents.33 Antipsychotic medications are also used to treat anxiety sympt o m ~ .A ' ~thorough risk-benefit analysis has not been conducted comparing antipsychotics and benzodiazepines. In general, the risk of physiologic dependence on benzodiazepines is perceived as less burdensome than the risk of developing involuntary movement disorder (tardive dyskinesia). Benzodiazepine withdrawal can be complicated. Patients with panic disorder are reported to have extreme difficulty discontinuing treatment. Klein et alZ9used carbamazepine (Tegretol) to mitigate the severity of withdrawal symptoms while discontinuing alprazolam (Xanax).In their double-blind (carbamazepine-placebo) study, this use assisted the patients with panic disorder but made little difference to those with GAD. All of the patients with panic disorder who received placebo were not able to complete the 4-week withdrawal phase and dropped out of the study. DEPRESSEDRESPONSES
Biologic Basis The noradrenergic theory of mood disorders was proposed in the 1960s.*,50 Mania was hypothesized as due to excess monoamines and
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depression resulting from an absence or relative lack of catecholamines, particularly noradrenaline. Projections of noradrenergic neurons extend from midline midbrain structures throughout subcortical and cortical areas, including cortex, limbic areas, thalamus, hypothalamus, cerebellum, sensory nuclei, and down into the spinal cord. Drugs that stimulate noradrenergic activity are not uniformly successful antidepressants. The serotoninergic theory proposes that a deficit of serotonin (in central nervous system) causes the onset of depressive mood.1o,43 Increased serotonin availability (e.g., by reuptake inhibition) alleviates symptoms, including decreased energy, sadness, impaired concentration, disrupted sleep, and poor self-image. In some theorists’ view, these neurotransmitter systems, which have closely overlapping circuits and receptor distributions, always are acting in concert with each other. In the early 1970s, cholinergic mechanismsz5and dopaminergic mechanismsMfor onset of depression were presented. It has been reported that cholinomimetic properties increase depressed mood and anergic response, especially in persons prone to depressions or with family history of depression. Dopamine metabolites are lower than normal in many patients showing psychomotor retardation and severe suicidal ideation, features of rnelancholic depression. Levels of noradrenaline have been reported increased and more variable in persons with melancholic-psychotic depression than in cont r o l ~Peripheral .~~ markers of presynaptic a-adrenergic, postsynaptic padrenergic, and 3H-imipramine receptors do not correlate well with mood states, and they do not predict groups of patients’ responses to drugs directed at these receptors. There are many studies of abnormalities of neuroendocrinologic changes in depression. This research has been prompted by knowledge of hypothalamic peptides that are regulated by monoamines affecting mood states, with widespread receptor distribution throughout the limbic system, in turn, controlling hypothalamic activity. Approximately half of patients with melancholic depression show depressed cortisol suppression to the dexamethasone test; in other words, they maintain an aberrantly raised level of cortisol during the day instead of a diurnal variation. To date, measures of hypothalamic-hypophysial-adrenal axis function do not predict response to treatment or longer-term outcomes.
Diagnosis The differential diagnosis of depressive disorders (see accompanying box) is complicated by personality characteristics and duration of symptoms. Criteria for major depression require that symptoms have lasted for more than 2 weeks. These include vegetative symptoms of sleep and appetite disturbance in addition to disturbance of mood and sensations of worthlessness and helplessness. The diagnosis of dysthymia is challenging because of being less pronounced in severity and lasting for months or years. Depression may be superimposed on dys-
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thymia or bipolar illness. Substance use, such as recurrent alcohol abuse or acute intoxication, may induce dangerous and impulsive self-destructive behavior with depressed feelings. In some cases, the substance use is a poor attempt to treat an underlying dysphoria. That is, it is a poor attempt because alcohol is a central nervous system depressant.
Diagnostic Categories of Depressive Disorders
Major depressive disorder: symptoms of depressed mood, disturbance in sleep, decreased concentration and attention, change in appetite and weight, anhedonia and anergia, feelings of helplessness and hopelessness, with or without suicidal ideation or intent must have been present for at least 2 weeks in the absence of another medical or psychiatric condition; may occur as discrete episode or recurrent episodes Dysthymia: persistent and pervasive feelings of sadness that are not as severe as major depressive disorder; tend to respond to similar treatments Bipolar disorder: characterized by distinct periods of depression and mania; may exhibit primarily depressed, manic, or mixed patterns; manic periods usually of shorter duration, with decreased sleep, increased energy, grandiose ideation, rapid thoughts and speech, irritability or hostility, impulsive expansive behavior in poor judgment (e.g., spending money the person does not have) Cyclothymia: less severe form of fluctuation between manic and depressed mood states; may occur in rapid succession to each other Mood disorder due to medical condition: depression can be directly traced to medical condition or treatment Substance-related mood disorder: depressed mood is induced by physiologic effects of direct ingestion of drug of abuse, medication, or exposure to a toxin
In general, females show increased rates for depressive responses beginning in middle school. Genetic and environmental factors appear to have a stronger influence on females throughout adolescence in the 51 Adolescents with development of depressive and anxious responses.24* depression and conduct disorder reported more limited social interactions and higher dissatisfaction than matched They reported negative views of their family climate. Having severe symptoms of depression as an adolescent predicted a two to three fold increased risk of having at least one major depressive episode in adult life, according to Pine et al.42 Personality traits of negative affect and anxiety may predispose 26 Coping styles may ameliorate tendencies to females to depre~sion.~, depression and may be sensitive to treatment in college students according to Hagerty and Williams.22In males with conduct problems and depressive symptoms, neither was predictive of overall outcome but
together resulted in problem outcomes in multiple areas of fun~tioning.~ Depression in adolescent girls was found to predict higher rates of marriage at a younger age and greater marital dissatisfaction.ls K W O ~ ~ ~ examined cognitive and psychodynamic influences on level of dysphoria in undergraduate college students. This study supported that hopelessness was reinforced by attributing control outside of one's self and turning against self. An analysis of morbidity resulting from anxiety and depression was reported by Allgulander.' Allgulander reviewed records in Sweden from 1973 through 1983 and found increased death rate (across the life span) in persons who had recently been hospitalized and had medical problems, with anxiety, depressive neurosis, or both. Although depression was associated with twice the risk of suicide as that of anxiety, both were substantial contributors to self-inflicted death in people from the ages of adolescence to 45 years. Lower socioeconomic status and lower levels of education were correlated with depression, obesity, and attempted suicide in adolesc e n t ~Additionally, .~~ depression may be expected as a secondary condition to other medical conditions, such as epilepsy. Dunn et all2 reported depression in 23% of adolescent patients with epilepsy. Case reports of depression in specific syndromes, such as Kleine-Levin syndr0me,3~remind the clinician of the presence of psychopathology in genetic disorders of metabolism and neurologic function. At least one study has found that depressive symptoms (including depressive disorder) are associated with smoking (cigarettes) in teenager^.'^ Treatment issues
Treatment strategies should be flexible and consistent with the individual's and family's belief systems. Supportive counseling or psychotherapy is indicated for stress reactions, brief reactive adjustment disorders, and adaptation to chronic disorders. Renaud et a146found that adolescents who responded to supportive and intensive psychotherapeutic measures had better outcomes and that a positive response could assist in determination of who should receive medication treatment for depression. Depressive symptoms may resolve with psychotherapy. Repetitive thinking and behaviors that lead to recurrent depressive or anxious thought patterns must be addressed to permit long-term healthy outcomes, beyond the acute treatment response. Cognitive behavior therapy is an effective and structured treatment approach to change habitual thinking and behavior.45 Psychotherapy techniques usually focus on the interpersonal meanings and interactions people engage in. Changes generally occur more slowly with these techniques than with medications but may be more fundamental in terms of increased personal awareness of factors that increase the person's well-being and selfaffirmation and that decrease tendencies toward self-deprecation and
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RECOGNIZING AND TREATING ANXIETY AND DEPRESSION IN ADOLESCENTS
self-blame. Often the physiologic arousal is interrupting attempts at verbalizing internal feeling states. Especially in these cases, pharmacologic treatment must be initiated for psychologic work to begin and to proceed. Medications for the treatment of depressive symptoms, with or without anxiety, are geared toward increasing serotoninergic activity or the noradrenergic system (Table 2). SSRIs are perhaps most easily tolerated. Although fluoxetine (Prozac) has been reported to contribute to suicide in early studies, it appears that the induction of restlessness (akathisia) unexpected and untreated is the cause of this driven behavior. All SSRIs may cause an awakening or sedating response, and the timing of ingestion should be arranged depending on the individual's response. SSRIs have a generally low rate of side effects, but the ones more frequently seen include prolongation of time to sexual climax; anorgasmia; gastric distress, with nausea, intestinal gas, or diarrhea; headaches; and weight gain or loss. Tricyclic antidepressants are effective agents for mixed anxiety and depression disorders and depression with prominent sleep disturbance and for people who are unable to tolerate SSRI side effects. Tricyclic antidepressants affect cardiac conduction and may cause profound orthostatic hypotension. A baseline electrocardiogram should be obtained to screen for subtle changes in cardiac conduction. Monoamine oxidase inhibitors are indicated in the treatment of atypical depression but must be used even more cautiously in adolescents than adults because of the need to monitor dietary restrictions (high tyramine containing foods may precipitate a hypertensive crisis). Adolescent women with reproductive capability should be counseled about the potential teratogenic effects of all medications, including tricyclic antidepressants. Concomitant substance abuse must be addressed simultaneously and the treatment efforts integrated with each other. Several studies Table 2. ANTIDEPRESSANT MEDICATIONS Drug Class
SSRI
Drug Name
Sertraline (Zoloft)
Dose (mg/d) 12.5-200
Paroxetine (Paxil) 10-50 Fluoxetine (Prozac) 10-60 Venlafaxine (Effexor) 37.5-375 Fluvoxamine (Luvox) 25-200 25-250 TCA Amitriptyline (Elavil) 25-250 Imipramine (Tofranil) Desipramine (Norpramin) 25-250 20-200 Nortriptyline (Pamelor) MA01 Phenelzine (Nardil) 15-45 Tranylcypromine (Parnate) 10-30
Comments Sedation, early in treatment; weight gain frequent Decreases anxiety Effective in bulimia; activating Little sedation Decreases obsessive-compulsive behavior Used in pain Decreases anxiety Metabolite of imipramine Alerting
SSRI = Selective serotonin-reuptakeinhibitor; TCA amine oxidase inhibitor.
=
tricyclic antidepressant; MA01
=
mono-
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have shown that substance abuse correlated with poor compliance after hospitalization and with low level of family s ~ p p o r t .23,~ ,35 At a minimum, these factors must raise the attention of the treatment teams.52 DETERMINING ACUITY AND IMPULSIVITY
Responsibility for determining the severity of symptoms lies with the examining professional. This responsibility includes assessment of suicidal intent and likelihood of attempting suicide. Factors that must be included in such an assessment are (1) imminent danger to self or others, awareness of danger, plans and access to means, and acute stressors; (2) social network and meaningfulness of connections and capacity for intimacy; (3) substance abuse or dependence-current intoxicated state, and likelihood of access to intoxicating drugs in immediate future; and (4)documentation of concerns, communications, and recommendations. The presence of reliable and supportive adults who can participate in providing means of access to treatment and preventing impulsive self-destructive acts are critical for outpatient management of unstable patients. Practitioners should not feel hesitant to request a second opinion from a trained colleague. Determination of suicidal risk can be murky, and the consequences of impulsive, rash acts are serious. Collaborative decision making is the best means of preventing unnecessary accident and death. SUMMARY
Recognition of depressive and anxiety disorders in adolescents reduces morbidity, mortality, and lifetime risk for psychiatric illness and maladaptive behaviors. Effective treatments for these disorders are available and are associated with minimal severe side effects. Because adolescents tend to underreport their psychologic distress, screening for these disorders in the primary care setting is incumbent on the Depression or anxiety may be a primary or a secondary condition-with each other and with other medical illness. Substance abuse, including cigarettes, should not be overlooked as an accompanying risk factor for poor health care habits and as an indicator of degree of family (lack of) support. Adolescents at risk should be screened and their symptoms taken seriously. This brief overview does not focus on the need for primary care clinicians to seek assistance and support of psychiatrists in the diagnosis and development of treatment algorithms. All clinicians should be reminded that judgments about peoples’ internal mental states and function are difficult to assess objectively and with compassion. Initial assessment in the primary care setting should include a telephone consultation with a reliable psychiatric colleague and referral for more in-depth evaluation in the event of more complicated course. These disorders
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need to be treated comprehensively because of the lifelong implications that having a chronic disease bear on the individual and his or her physiology. Primary care clinicians are pivotal instruments in engaging adolescents to embrace appropriate therapeutic measures for their current and future health.
References 1. Allgulander C: Suicide and mortality patterns in anxiety neurosis and depressive neurosis. Arch Gen Psychiatry 51:708-712, 1994 2. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4 (DMS-IV). Washington, DC, American Psychiatric Association Press, 1994 3. Aseltine RH Jr, Gore S, Colten ME: The co-occurrence of depression and substance abuse in late adolescence. Dev Psychopathol 10:549-570, 1998 4. Bardone AM, Moffitt TE, Caspi A, et al: Adult physical health outcomes of adolescent girls with conduct disorder, depression, and anxiety. J Am Acad Child Adolesc Psychiatry 37594601, 1998 5. Biederman J, Rosenbaum JF, Bolduc-Murphy EA, et al: A 3-year follow-up of children with and without behavioral inhibition. J Am Acad Child Adolesc Psychiatry 323814821, 1993 6. Bird HR, Gould MS, Staghezza BM: Patterns of diagnostic comorbidity in a community sample of children aged 9 through 16 years. J Am Acad Child Adolesc Psychiatry 32361368, 1993 7. Bouhuys AL, Geerts E, Gordijn MC: Gender-specific mechanisms associated with outcome of depression: Perception of emotions, coping and interpersonal functioning. Psychiatry Res 85:247-261, 1999 8. Bunney WF Jr, Davis JB: Norepinephrine in depressive reactions: A review. Arch Gen Psychiatry 13:483-494, 1965 9. Capaldi DM, Stoolmiller M Co-occurrence of conduct problems and depressive symptoms in early adolescent boys: 111. Prediction to young-adult adjustment. Dev Psychopathol 11:59-84, 1999 10. Coppen AJ, Dougan DP: Serotonin and its place in the pathogenesis of depression. J Clin Psychiatry 49:4-11, 1988 11. den Boer JA, Westenberg HG, De Leeuw AS, et al: Biological dissection of anxiety disorders: The clinical role of selective serotonin reuptake inhibitors with particular reference to fluvoxamine. Int Clin Psychopharmacol 9:47-52, 1995 12. Dunn DW, Austin JK, Huster GA: Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry 38:1132-1138, 1999 13. Eke M, McNally RJ: Anxiety sensitivity, suffocation fear, trait anxiety, and breathholding duration as predictors of response to carbon dioxide challenge. Behav Res Ther 34:603-607, 1996 14. El-Khayat R, Baldwin D S htipsychotic drugs for non-psychotic patients: Assessment of the benefit / risk ratio in generalized anxiety disorder. J Psychopharmacol 12323329, 1998 15. Escobedo LG, Reddy M, Giovino GA: The relationship between depressive symptoms and cigarette smoking in US adolescents. Addiction 93:433-440, 1998 16. Goldberg C: Cognitive-behavioral therapy for panic: Effectiveness and limitations. Psychiatr Q 692344, 1998 17. Goodman E: The role of socioeconomic status gradients in explaining differences in US adolescents’ health. Am J Public Health 89:1522-1528, 1999 18. Gotlib IH, Lewinsohn PM, Seeley J R Consequences of depression during adolescence: Marital status and marital functioning in early adulthood. J Abnorm Psycho1 107:868890, 1998 19. Gray J A Drug effects on fear and frustration: Possible limbic site of action of minor
904
REEVE
tranquilizers. In Iverson LL, Iverson SD, Snyder SH (eds): Handbook of Psychopharmacology. New York, Plenum, 1977, pp 433-529 20. Gray JA: The Psychology of Fear and Stress, ed 2. Cambridge, Cambridge University Press, 1987 21. Gray JA: A model of the limbic system and basal ganglia: Applications to anxiety and schizophrenia. In Gazzaniga MS (ed): The Cognitive Neurosciences. Cambridge, MA, MIT Press, 1995, pp 1165-1176 22. Hagerty BM, Williams RA: The effects of sense of belonging, social support, conflict, and loneliness and depression. Nurs Res 48:215-219, 1999 23. Hoffman JP, Su S S Stressful life events and adolescent substance use and depression: Conditional and gender differentiated effects. Subst Use Misuse 33:2219-2262, 1998 24. Jacobson KC, Rowe DC: Genetic and environmental influences on the relationships between family connectedness, school connectedness and adolescent depressed mood: sex differences. Dev Psychol 35:926-939, 1999 25. Janowsky DS, El Yousef MK, Davis JM: A cholinergic-adrenergic hypothesis of depression and mania. Lancet 2:6732-6735, 1972 26. Joiner TE Jr, Blalock JA, Wagner KD: Preliminary examination of sex differences in depressive symptoms among adolescent psychiatric inpatients: The role of anxious symptoms and generalized negative affect. J Clin Child Psychol 28:211-219, 1999 27. Kelly CB, Cooper SJ: Differences and variability in plasma noradrenaline between depressive and anxiety disorders. J Psychopharmacol 12161-167, 1998 28. Kessler D, Lloyd K, Lewis G, et al: Cross sectional study of symptom attribution and recognition of depression and anxiety in primary care. BMJ 3B436-439, 1999 29. Klein E, Colin V, Stolk J, et al: Alprazolam withdrawal in patients with panic disorder and generalized anxiety disorder: Vulnerability and effect of carbamazepine. Am J Psychiatry 151:1760-1766, 1994 30. Kramer T, Garralda ME: Psychiatric disorders in adolescents in primary care. Br J Psychiatry 173:508-513, 1998 31. Kroenke K, Spitzer RL, Williams JB, et al: Physical symptoms in primary care: Predictors of psychiatric disorders and functional impairment. Arch Fam Med 33774-779, 1994 32. Kwon P: Attributional style and psychodynamic defense mechanisms: Towards an integrative model of depression. J Pers 67645-658, 1999 33. Labbate LA: Sex and serotonin reuptake inhibitor antidepressants. Psychiatr AM 29:571-579, 1999 34. Lecrubier Y, Ustun TB: Panic and depression: A worldwide primary care perspective. Int Clin Psychopharmacol 13:7-11, 1998 35. Lloyd A, Horan WK, Borgar SR, et al: Predictors of medication compliance after hospital discharge in adolescent psychiatric patients. J Child Adolesc Psychopharmacol 81133-141, 1998 36. Lynskey MT, Fergusson DM, Horwood LJ: The effect of parental alcohol problems on rates of adolescent psychiatric disorders. Addiction 89:1277-1286, 1994 37. McConaughy SH, Achenbach TM: Comorbidity of empirically based syndromes in matched general population and clinical samples. J Chilh Psychol Psychiatry 35:11411157, 1994 38. Monck E, Graham P, Richman N, et al: Adolescent girls: 11. Background factors in anxiety and depressive states. Br J Psychiatry 165:770-780, 1994 39. Mukaddes NM, Alyanak B, Kora ME, et al: The psychiatric symptomatology in KleineLevin syndrome. Child Psychiatry Hum Dev 29:253-258, 1999 40. Ollendick TH, Mattis SG, King NJ: Panic in children and adolescents: A review. J Child Psychol Psychiatry 35:113-134, 1994 41. Olsson GI, Nordstrom ML, Arinell H, et al: Adolescent depression: Social network and family climate-a case control study. J Child Psychol Psychiatry 40:227-237, 1999 42. Pine DS, Cohen E, Cohen P, et al: Adolescent depressive symptoms as predictors of adult depression: Moodiness or mood disorder? Am J Psychiatry 156:133-135, 1999 43. Prange AJ Jr, Wilson IC, Lynn CW: L-tryptophan in mania: Contribution to a permissive hypothesis of affective disorders. Arch Gen Psychiatry 30:5&62, 1974
RECOGNIZING AND TREATING ANXIETY AND DEPRESSION IN ADOLESCENTS
905
44. Radrup A, Munkvad I, Fog R Mania, Depression and Brain Dopamine: Current Developments in Psychopharmacology. New York, Spectrum, 1975 45. Reinecke MA, Ryan NE, DuBois DL: Cognitive-behavioral therapy of depression and depressive symptoms during adolescence: A review and meta-analysis. J Am Acad Child Adolesc Psychiatry 37:26-34, 1998 46. Renaud J, Brent DA, Baugher M, et al: Rapid response to psychosocial treatment for adolescent depression: A two-year follow-up. J Am Acad Child Adolesc Psychiatry 37:1184-1190, 1998 47. Roy-Byrne P, Cowley DS, Stein MB, et al: Cardiovascular and catecholamine response to orthostasis in panic and obsessive-compulsive disorder and normal controls: effects of anxiety and novelty. Depress Anxiety 6:159-164, 1997 48. Rudd MD, Joiner T The role of symptom induction in the treatment of panic and anxiety: Identifiable domains, conditional properties, and treatment targets. Behav Modif 22:9&107, 1998 49. Scott L, OHara MW: Self-discrepancies in clinically anxious and depressed university students. J Abnorm Psycho1 102:282-287, 1993 50. Schildkraut J: The catecholamine hypothesis of affective disorders: A review of supporting evidence. Am J Psychiatry 113:1407-1411, 1965 51. Schraedley PK, Gotlib IH, Hayward C: Gender differences in correlates of depressive symptoms in adolescents. J Adolesc Health 25:98-108, 1999 52. Zeitlin H: Psychiatric comorbidity with substance misuse in children and teenagers. Drug Alcohol Depend 55:225-234, 1999
Address reprint requests to Alya Reeve, MD Department of Psychiatry UNMHSC 2400 Tucker, NE Albuquerque, NM 87131
e-mail: [email protected]