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A review of randomized, controlled medication trials for major depression
188A
BIOL PSYCHIATRY 1992;3I:61A-252A
Treatment of Affective Disorders
294 DIFFERENTIAL EFFECTS OF SELECTIVE AND NONSELECTIVE ANTIDEPRESSANTS ON CARDIOVASCULAR RESPONSES TO STANDING Sue Wilson, Nick Coupland, Paul Glue, David J. Nutt School of Medical Sciences, Bristol, BS28HW, UK. To examine the mechanisms underlying antidepressant t'AD)-induced postural hypotension, we have studied
BP and HR responses to standing in a series of patient.~ with DSM-III-R major depression or panic anxiety before and during treatment with selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine), nonselective RIs (e.g., imipramine), and MAOIs (e.g., phenelzine). BP and HR were measured using a beat-tobeat finger photopiethysmography technique (Finapres). The fall in systolic and diastolic BP and compensatory increase in HR after standing are exaggerated and prolonged by nonselective Rls. In comparison, selective Rls have much smaller effects on postural BP and HR changes. The effects of phenelzine are marked and resemble those of imipramine. The use ol the Finapres technique for continuous noninvasive monitoring of CVS measures represents a major advance in assessing the unwanted effects of psychotropic agents and should improve our understanding of the neuropharmacological basis of autonomic nervous system control.
295 THE EFFECTIVENESS OF DRUG TREATMENT IN DEPRESSED PATIENTS Avner Elizur, Zipora Bar, Henry Szor, Yona Teichman Tel-Aviv University, Israel. The present study evaluated and specified the benefits of combining cognitive therapy or marital therapy with drug treatment as opposed to drug treatment nlone, in depressed patients. Sixty patients suffering from major depression or dysthymic disorder according to DSM-III-R criteria were selected. The patients were married and between 25 and 55 years old. They were divided into four matched groups according to diagnoses, gender, age, and socioeconomic level. Treatment was week by week for 10-15 weeks, by trained psychotherapists. Follow-up evaluation was done 6 months later. Scales for depression, marital satisfaction, hostility, self-concept, and functional activity were used. Results indicate that all treatment modalities were significantly effective at the end of the treatment period. This was apparent in four of five dimensions: level of depression, self esteem, hostility, and functioning. The 6-month follow-up evaluation demonstrated a significantly better effect of the combination of drug treatment with psychotherapy as opposed to drug treatment alone. Combination of marital theraD' and drug treatment, however, was significantly superior to the combination of cognitive therapy and drug treatment and to drug treatment alone. This was apparent, especially in three dimensions: le/el of depression, self-esteem, and marital satisfaction. This was true on termination and after 6-month follow-up. Although all modalities were effective at termination, the combination of drug and psychotherapy had a longer-lasting effect, most significantly, marital therapy and drug treatment.
296 A REVIEW OF RANDOMIZED, CONTROLLED MEDICATION TRIALS FOR MAJOR DEPRESSION Madukar Trivedi, A. John Rush University of Texas Southv,estern Medical Center at Dallas, Dallas, TX 75235-9070. As part of the required background r,v!ew to develop clinical practice guidelines for primary care physicians, we conducted a rigorous scientific review and metaanalyses, where feasible, on all published, randomized controlled medication trials for major depression since 1975. Most trials were acute (4-8 weeks) and conducted in adults. A modest number (n = 37) were found for geriatric patients, and even fewer (n =
Mood Disorders
BIOL PSYCHIATRY 1992;31:61A-252A
189A
8) were found for children/adolescents. Nearly all continuation (n = 26) or maintenance trials were open/ nonrandomized. Many studies could not be included in the metaanalyses due to deficiencies in what was reported in the articles. These deficits will be reviewed. Suggestions for improvements in reporting results of a randomized, controlled trial will be made. Factors affecting placebo response will be discussed.
297 A CONTROLLED TRIAL OF TRAZODONE FOR ANTIDEPRESSANT-ASSOCIATED INSOMNIA Andrew A. Nierenberg, Lenard A. Adler, Eric Peselow, Gwen Zornberg, Michel Rosenthal Harvard Medical School, McLean Hospital, Belmont, MA 02178. Up to 50% of patients receiving nonsedating antidepressants, such as fluoxetine, bupropion, and MAOI's, may have persistent insomnia, in spite of a response in depressive symptoms. We present preliminary results of the first placebo-controlled, double-blind trial of trazodone in the management of antidepressant-associated insomnia. Fifteen subjects were randomized to treatment for 2-8 days with either trazodone 50-100 mg QHS or matching placebo and were crossed-over to treatment with the alternative pills for another 2 to 8 day epoch. Sleep measures included the modified Pittsburgh Sleep Quality Index (PSQI) and the sleep items of the Yale-New Haven Hospital Depressive Symptom Inventory (YNH). Subjects reported improvement in several sleep measures with trazodone as compared with placebo (specifically with mean improvement in PSQI sleep duration, total PSQI, YNH middle-night and early-morning awakenings, and total YNH sleep score statistically better with trazodone). Subjective sleep quality and sleep latency had a trend toward improvement (p < 0.06), but there were no improvements noted for sleep efficiency or sleep disturbances on PSQI components and no improvement in difficulty falling asleep on the YNH item. Trazodone is an effective hypnotic for antidepressant-associated insomnia as compared with placebo on subjective measures of sleep. Further studies using polysomnography are necessary to confirm these findings.
PLENARY SESSION MOOD DISORDERS Saturday, May 2, 8:30-11:30 AM
Ballroom
298 DEVELOPMENTAL NEUROENDOCRINOLOGY: HORMONES SHAPE SEX DIFFERENCES AS WELL AS INDIVIDUAL TRA1TS Bruce S. McEwen Rockefeller University, New York, NY i0021. The neuroendocrine system develops before birth and participates in shaping both individual and group, that is, sex, differences. Thyroid hormone excess at birth in rats alters morphological and neurochemical development of basal forebrain and hippocampus, whereas testosterone alters brain structure and programming of responses to hormones during adult life, including reproductive centers such as hypothalamus and also the hippocampus. These effects are permanent. Adrenal steroids participate in normal development of the dentate gyms of the hippocampal formation via effects on neuron death and survival, and chronic stress leads to atrophy of neurons within the hippocampus. All of these effects occur via intracellular DNAbinding hormone receptors that alter gene expression. Sex differences and thyroid effects are programmed as part of the developmental process. Variations in hormone levels during this process can lead to individual differences. Stress effects represent a means tbr experience to impact upon the brain.
BIOL PSYCHIATRY 1992;3I:61A-252A
Treatment of Affective Disorders
294 DIFFERENTIAL EFFECTS OF SELECTIVE AND NONSELECTIVE ANTIDEPRESSANTS ON CARDIOVASCULAR RESPONSES TO STANDING Sue Wilson, Nick Coupland, Paul Glue, David J. Nutt School of Medical Sciences, Bristol, BS28HW, UK. To examine the mechanisms underlying antidepressant t'AD)-induced postural hypotension, we have studied
BP and HR responses to standing in a series of patient.~ with DSM-III-R major depression or panic anxiety before and during treatment with selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine), nonselective RIs (e.g., imipramine), and MAOIs (e.g., phenelzine). BP and HR were measured using a beat-tobeat finger photopiethysmography technique (Finapres). The fall in systolic and diastolic BP and compensatory increase in HR after standing are exaggerated and prolonged by nonselective Rls. In comparison, selective Rls have much smaller effects on postural BP and HR changes. The effects of phenelzine are marked and resemble those of imipramine. The use ol the Finapres technique for continuous noninvasive monitoring of CVS measures represents a major advance in assessing the unwanted effects of psychotropic agents and should improve our understanding of the neuropharmacological basis of autonomic nervous system control.
295 THE EFFECTIVENESS OF DRUG TREATMENT IN DEPRESSED PATIENTS Avner Elizur, Zipora Bar, Henry Szor, Yona Teichman Tel-Aviv University, Israel. The present study evaluated and specified the benefits of combining cognitive therapy or marital therapy with drug treatment as opposed to drug treatment nlone, in depressed patients. Sixty patients suffering from major depression or dysthymic disorder according to DSM-III-R criteria were selected. The patients were married and between 25 and 55 years old. They were divided into four matched groups according to diagnoses, gender, age, and socioeconomic level. Treatment was week by week for 10-15 weeks, by trained psychotherapists. Follow-up evaluation was done 6 months later. Scales for depression, marital satisfaction, hostility, self-concept, and functional activity were used. Results indicate that all treatment modalities were significantly effective at the end of the treatment period. This was apparent in four of five dimensions: level of depression, self esteem, hostility, and functioning. The 6-month follow-up evaluation demonstrated a significantly better effect of the combination of drug treatment with psychotherapy as opposed to drug treatment alone. Combination of marital theraD' and drug treatment, however, was significantly superior to the combination of cognitive therapy and drug treatment and to drug treatment alone. This was apparent, especially in three dimensions: le/el of depression, self-esteem, and marital satisfaction. This was true on termination and after 6-month follow-up. Although all modalities were effective at termination, the combination of drug and psychotherapy had a longer-lasting effect, most significantly, marital therapy and drug treatment.
296 A REVIEW OF RANDOMIZED, CONTROLLED MEDICATION TRIALS FOR MAJOR DEPRESSION Madukar Trivedi, A. John Rush University of Texas Southv,estern Medical Center at Dallas, Dallas, TX 75235-9070. As part of the required background r,v!ew to develop clinical practice guidelines for primary care physicians, we conducted a rigorous scientific review and metaanalyses, where feasible, on all published, randomized controlled medication trials for major depression since 1975. Most trials were acute (4-8 weeks) and conducted in adults. A modest number (n = 37) were found for geriatric patients, and even fewer (n =
Mood Disorders
BIOL PSYCHIATRY 1992;31:61A-252A
189A
8) were found for children/adolescents. Nearly all continuation (n = 26) or maintenance trials were open/ nonrandomized. Many studies could not be included in the metaanalyses due to deficiencies in what was reported in the articles. These deficits will be reviewed. Suggestions for improvements in reporting results of a randomized, controlled trial will be made. Factors affecting placebo response will be discussed.
297 A CONTROLLED TRIAL OF TRAZODONE FOR ANTIDEPRESSANT-ASSOCIATED INSOMNIA Andrew A. Nierenberg, Lenard A. Adler, Eric Peselow, Gwen Zornberg, Michel Rosenthal Harvard Medical School, McLean Hospital, Belmont, MA 02178. Up to 50% of patients receiving nonsedating antidepressants, such as fluoxetine, bupropion, and MAOI's, may have persistent insomnia, in spite of a response in depressive symptoms. We present preliminary results of the first placebo-controlled, double-blind trial of trazodone in the management of antidepressant-associated insomnia. Fifteen subjects were randomized to treatment for 2-8 days with either trazodone 50-100 mg QHS or matching placebo and were crossed-over to treatment with the alternative pills for another 2 to 8 day epoch. Sleep measures included the modified Pittsburgh Sleep Quality Index (PSQI) and the sleep items of the Yale-New Haven Hospital Depressive Symptom Inventory (YNH). Subjects reported improvement in several sleep measures with trazodone as compared with placebo (specifically with mean improvement in PSQI sleep duration, total PSQI, YNH middle-night and early-morning awakenings, and total YNH sleep score statistically better with trazodone). Subjective sleep quality and sleep latency had a trend toward improvement (p < 0.06), but there were no improvements noted for sleep efficiency or sleep disturbances on PSQI components and no improvement in difficulty falling asleep on the YNH item. Trazodone is an effective hypnotic for antidepressant-associated insomnia as compared with placebo on subjective measures of sleep. Further studies using polysomnography are necessary to confirm these findings.
PLENARY SESSION MOOD DISORDERS Saturday, May 2, 8:30-11:30 AM
Ballroom
298 DEVELOPMENTAL NEUROENDOCRINOLOGY: HORMONES SHAPE SEX DIFFERENCES AS WELL AS INDIVIDUAL TRA1TS Bruce S. McEwen Rockefeller University, New York, NY i0021. The neuroendocrine system develops before birth and participates in shaping both individual and group, that is, sex, differences. Thyroid hormone excess at birth in rats alters morphological and neurochemical development of basal forebrain and hippocampus, whereas testosterone alters brain structure and programming of responses to hormones during adult life, including reproductive centers such as hypothalamus and also the hippocampus. These effects are permanent. Adrenal steroids participate in normal development of the dentate gyms of the hippocampal formation via effects on neuron death and survival, and chronic stress leads to atrophy of neurons within the hippocampus. All of these effects occur via intracellular DNAbinding hormone receptors that alter gene expression. Sex differences and thyroid effects are programmed as part of the developmental process. Variations in hormone levels during this process can lead to individual differences. Stress effects represent a means tbr experience to impact upon the brain.