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Pharmacological Treatment of Posttraumatic Stress Disorder
JNP
Pharmacological Treatment of Posttraumatic Stress Disorder Posttraumatic stress disorder (PTSD) is a complex disorder resulting from severe psychic trauma. The three core symptoms are re-experience of the trauma in flashbacks or dreams, avoidance of remembering, and increased arousal. PTSD may be accompanied by distress with cues that resemble the event, loss of interest in things, numbness, irritability,
PRESCRIPTION PAD Maren S. Mayhew, MS, ANP, GNP hypervigilance, difficulty with interpersonal relationships, somatic complaints, depression, mood swings, psychotic symptoms, aggression, impulsivity, and anxiety. Symptoms may be divided into positive symptoms (arousal and re-experiencing) and negative (avoidance, numbing, and withdrawal). Chronic PTSD usually occurs with other mood disorders, such as depression, anxiety, and substance abuse.1 PTSD is considered acute if symptoms are present for 1 to 3 months. PTSD is labeled chronic with symptoms recurring for more than 3 months. The average duration of symptoms is more than 7 years but may last for decades.1 The lifetime prevalence of PTSD in the US is surprisingly high, approximately 10%. The prevalence of PTSD in deployed soldiers is approximately 25%. Symptoms are usually nonspecific and difficult to diagnose. The level of distress in all these individuals may seem high compared to their symptomatology. Patients may not even realize the connection between the traumatic event and their symptoms.2
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The Journal for Nurse Practitioners - JNP
Treatment of PTSD is multidisciplinary and includes nonpharmacological treatment whenever available. Many types of psychotherapy have been used in the treatment of PTSD. The combination of medication and psychotherapy is widely used. Pharmacotherapy may ameliorate the symptoms that interfere with psychotherapy. The goal of therapy is stabilization, not cure. Other treatment goals could be improved sleep, control of emotional reactions, and reduced substance abuse.2 Over the years, just about every psychotropic medication has been tried to treat PTSD. No medication has been shown to be effective in preventing or curing PTSD, although few have had rigorous testing for this indication. Most drug research for PTSD has been done on male combat veterans. A Cochrane Review demonstrated the efficacy of medication in the shortterm treatment of PTSD; they are effective for treatment of the three cardinal symptoms of PTSD, accompanying symptoms, and overall improvement in quality of life.3 The medications most researched in PTSD are selective serotonin reuptake inhibitors (SSRIs); therefore they are considered first-line treatment. They are helpful for the three core symptoms listed above. SSRIs are generally started at a low dose and titrated gradually. If one SSRI is not effective, another may be tried. The response rate is approximately 60% and remission rate is approximately 20%. Medication should be continued for at least a year to prevent relapse.2 Other antidepressants may also be used. Antidepressants may be useful in treating the negative symptoms of PTSD. Tricyclic antidepressants are useful to decrease the nightmares and flashbacks, but they are generally given in low doses that are not effective for treating depression. Monoamine oxidase inhibitors (MAOIs) may be
Volume 7, Issue 3, March 2011
effective for the symptom of re-experiencing the trauma. However, they have side effects and dietary restrictions that limit their use. Other antidepressants such as serotonin norepinephrine inhibitors (SNRIs) have not been researched for PTSD.2 Anticonvulsants may be used as mood stabilizers. Carbamazepine, valproic acid, and lamotrigine may be effective for the symptoms of re-experiencing and hyperarousal, but adequate research has not been conducted.2 The alpha blocker prazosin has been effective in decreasing nightmares but not other symptoms of PTSD in a few small studies. Side effects of prazosin include orthostasis, headache, and lethargy. Palpitations, nervousness, headache, edema, dizziness, edema, and blurred vision have occurred. Syncope and first dose effect may occur. Priapism occurs rarely. Leukopenia/neutropenia has rarely occurred.4 Atypical antipsychotics are used if SSRIs are not effective. Olanzapine (Zyprexa), a second generation antipsychotic, has been the most frequently used antipsychotic by the military.5 Compared to other antipsychotics, olanzapine has increased risk for weight gain and dyslipidemia but decreased risk of extra-pyramidal effects and prolactinemia.6 Common adverse reactions are somnolence, extrapyramidal symptoms, dizziness, headache, fatigue, insomnia, weight gain, increased appetite, xerostomia, constipation, dyspepsia, and weakness.4 Olanzapine may alter cardiac conduction, causing life-threatening arrhythmias. It may cause anticholinergic effects such as constipation, xerostomia, blurred vision, urinary retention. Blood dyscrasias such as leukopenia, neutropenia, and agranulocytosis, which can be fatal, may also occur. Extrapyramidal symptoms include Parkinsonism, dystonia, akathisia, and tardive dyskinesia. Olanzapine has an increased risk of hyperglycemia that can be associated with ketoacidosis, hyperosmolar coma, and death. Increases in cholesterol and triglycerides have occurred. Hyperprolactinemia may occur. Neuroleptic malignant syndrome with mental status changes, fever, muscle rigidity, and autonomic instability may occur. The drug may cause orthostatic hypotension and sedation. Impaired core body temperature regulation may occur. Weight can be a significant problem. These symptoms require monitoring of vital www.npjournal.org
signs, lipids, blood glucose, hepatic enzymes, body mass index, orthostatic blood pressure, mental status, abnormal involuntary movements, and extrapyramidal symptoms.4 Benzodiazepines generally should be avoided for PTSD. They are less effective than might be expected for the symptoms of hyperarousal and anxiety. There is a high comorbidity of substance abuse with PTSD, and benzodiazepines are prone to abuse.1 PTSD is more common in primary care than is usually recognized. It is very difficult to treat. Treatment should focus on nonpharmacologic modes, with medications as a useful adjunct to psychotherapy. SSRIs are considered first line medication, with the atypical antipsychotic olanzapine tried if SSRIs are not effective. References 1. Nakell L. Adult post-traumatic stress disorder: Screening and treating in primary care. Prim Care Clin Office Pract. 2007;34:593-610. 2. Shalev A. Posttraumatic stress disorder and stress-related disorders. Psychiatr Clin N Am. 2009;32:687-704. 3. Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD002795. DOI: 10.1002/14651858.CD002795.pub2. 4. Edmunds MW, Mayhew MS. Pharmacology for the Primary Care Provider. 3rd ed. St. Louis: Mosby; 2009. 5. Stein MB, Kline NA, Matloff JL. Adjunctive olanzapine for SSRIresistant combat-related PTSD: A double-blind, placebo-controlled study. Am J Psychiatry. 2002;159:1777-1779. 6. Kantrowitz JT. Olanzapine: review of safety 2008. Expert Opin Drug Saf. 2008;7(6):761-769.
Maren Mayhew, MS, ANP, GNP, is the author and editor of Pharmacology for Primary Care Providers, a textbook for NPs published by Mosby. She can be reached at marenmayhew @comcast.net. Suggestions for topics are welcome.
1555-4155/11/$ see front matter © 2011 American College of Nurse Practitioners doi:10.1016/j.nurpra.2011.01.008
The Journal for Nurse Practitioners - JNP
237
Pharmacological Treatment of Posttraumatic Stress Disorder Posttraumatic stress disorder (PTSD) is a complex disorder resulting from severe psychic trauma. The three core symptoms are re-experience of the trauma in flashbacks or dreams, avoidance of remembering, and increased arousal. PTSD may be accompanied by distress with cues that resemble the event, loss of interest in things, numbness, irritability,
PRESCRIPTION PAD Maren S. Mayhew, MS, ANP, GNP hypervigilance, difficulty with interpersonal relationships, somatic complaints, depression, mood swings, psychotic symptoms, aggression, impulsivity, and anxiety. Symptoms may be divided into positive symptoms (arousal and re-experiencing) and negative (avoidance, numbing, and withdrawal). Chronic PTSD usually occurs with other mood disorders, such as depression, anxiety, and substance abuse.1 PTSD is considered acute if symptoms are present for 1 to 3 months. PTSD is labeled chronic with symptoms recurring for more than 3 months. The average duration of symptoms is more than 7 years but may last for decades.1 The lifetime prevalence of PTSD in the US is surprisingly high, approximately 10%. The prevalence of PTSD in deployed soldiers is approximately 25%. Symptoms are usually nonspecific and difficult to diagnose. The level of distress in all these individuals may seem high compared to their symptomatology. Patients may not even realize the connection between the traumatic event and their symptoms.2
236
The Journal for Nurse Practitioners - JNP
Treatment of PTSD is multidisciplinary and includes nonpharmacological treatment whenever available. Many types of psychotherapy have been used in the treatment of PTSD. The combination of medication and psychotherapy is widely used. Pharmacotherapy may ameliorate the symptoms that interfere with psychotherapy. The goal of therapy is stabilization, not cure. Other treatment goals could be improved sleep, control of emotional reactions, and reduced substance abuse.2 Over the years, just about every psychotropic medication has been tried to treat PTSD. No medication has been shown to be effective in preventing or curing PTSD, although few have had rigorous testing for this indication. Most drug research for PTSD has been done on male combat veterans. A Cochrane Review demonstrated the efficacy of medication in the shortterm treatment of PTSD; they are effective for treatment of the three cardinal symptoms of PTSD, accompanying symptoms, and overall improvement in quality of life.3 The medications most researched in PTSD are selective serotonin reuptake inhibitors (SSRIs); therefore they are considered first-line treatment. They are helpful for the three core symptoms listed above. SSRIs are generally started at a low dose and titrated gradually. If one SSRI is not effective, another may be tried. The response rate is approximately 60% and remission rate is approximately 20%. Medication should be continued for at least a year to prevent relapse.2 Other antidepressants may also be used. Antidepressants may be useful in treating the negative symptoms of PTSD. Tricyclic antidepressants are useful to decrease the nightmares and flashbacks, but they are generally given in low doses that are not effective for treating depression. Monoamine oxidase inhibitors (MAOIs) may be
Volume 7, Issue 3, March 2011
effective for the symptom of re-experiencing the trauma. However, they have side effects and dietary restrictions that limit their use. Other antidepressants such as serotonin norepinephrine inhibitors (SNRIs) have not been researched for PTSD.2 Anticonvulsants may be used as mood stabilizers. Carbamazepine, valproic acid, and lamotrigine may be effective for the symptoms of re-experiencing and hyperarousal, but adequate research has not been conducted.2 The alpha blocker prazosin has been effective in decreasing nightmares but not other symptoms of PTSD in a few small studies. Side effects of prazosin include orthostasis, headache, and lethargy. Palpitations, nervousness, headache, edema, dizziness, edema, and blurred vision have occurred. Syncope and first dose effect may occur. Priapism occurs rarely. Leukopenia/neutropenia has rarely occurred.4 Atypical antipsychotics are used if SSRIs are not effective. Olanzapine (Zyprexa), a second generation antipsychotic, has been the most frequently used antipsychotic by the military.5 Compared to other antipsychotics, olanzapine has increased risk for weight gain and dyslipidemia but decreased risk of extra-pyramidal effects and prolactinemia.6 Common adverse reactions are somnolence, extrapyramidal symptoms, dizziness, headache, fatigue, insomnia, weight gain, increased appetite, xerostomia, constipation, dyspepsia, and weakness.4 Olanzapine may alter cardiac conduction, causing life-threatening arrhythmias. It may cause anticholinergic effects such as constipation, xerostomia, blurred vision, urinary retention. Blood dyscrasias such as leukopenia, neutropenia, and agranulocytosis, which can be fatal, may also occur. Extrapyramidal symptoms include Parkinsonism, dystonia, akathisia, and tardive dyskinesia. Olanzapine has an increased risk of hyperglycemia that can be associated with ketoacidosis, hyperosmolar coma, and death. Increases in cholesterol and triglycerides have occurred. Hyperprolactinemia may occur. Neuroleptic malignant syndrome with mental status changes, fever, muscle rigidity, and autonomic instability may occur. The drug may cause orthostatic hypotension and sedation. Impaired core body temperature regulation may occur. Weight can be a significant problem. These symptoms require monitoring of vital www.npjournal.org
signs, lipids, blood glucose, hepatic enzymes, body mass index, orthostatic blood pressure, mental status, abnormal involuntary movements, and extrapyramidal symptoms.4 Benzodiazepines generally should be avoided for PTSD. They are less effective than might be expected for the symptoms of hyperarousal and anxiety. There is a high comorbidity of substance abuse with PTSD, and benzodiazepines are prone to abuse.1 PTSD is more common in primary care than is usually recognized. It is very difficult to treat. Treatment should focus on nonpharmacologic modes, with medications as a useful adjunct to psychotherapy. SSRIs are considered first line medication, with the atypical antipsychotic olanzapine tried if SSRIs are not effective. References 1. Nakell L. Adult post-traumatic stress disorder: Screening and treating in primary care. Prim Care Clin Office Pract. 2007;34:593-610. 2. Shalev A. Posttraumatic stress disorder and stress-related disorders. Psychiatr Clin N Am. 2009;32:687-704. 3. Stein DJ, Ipser JC, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD002795. DOI: 10.1002/14651858.CD002795.pub2. 4. Edmunds MW, Mayhew MS. Pharmacology for the Primary Care Provider. 3rd ed. St. Louis: Mosby; 2009. 5. Stein MB, Kline NA, Matloff JL. Adjunctive olanzapine for SSRIresistant combat-related PTSD: A double-blind, placebo-controlled study. Am J Psychiatry. 2002;159:1777-1779. 6. Kantrowitz JT. Olanzapine: review of safety 2008. Expert Opin Drug Saf. 2008;7(6):761-769.
Maren Mayhew, MS, ANP, GNP, is the author and editor of Pharmacology for Primary Care Providers, a textbook for NPs published by Mosby. She can be reached at marenmayhew @comcast.net. Suggestions for topics are welcome.
1555-4155/11/$ see front matter © 2011 American College of Nurse Practitioners doi:10.1016/j.nurpra.2011.01.008
The Journal for Nurse Practitioners - JNP
237