Marshall E. Cates

Baclofen Treatment for Chronic Posttraumatic Stress Disorder

OBJECTIVE: Previous studies have shown the efficacy of γ-aminobutyric acid B (GABAB) receptor agonists in treating anxiety in patients with panic disorder and in treating depression and anxiety in alcoholic patients. We hypothesized that baclofen, a GABAB agonist, would be an effective treatment in the symptomatic management of veterans with chronic posttraumatic stress disorder (PTSD). METHODS: Fourteen male veterans with chronic, combat-related PTSD were enrolled in an open-label, 8-week, monotherapy trial of baclofen titrated to a maximum of 80 mg/d in 3 divided doses. The primary outcome measure was the Clinician-Administered PTSD Scale (CAPS), and secondary outcome measures included the Hamilton Rating Scale for Anxiety, the Hamilton Rating Scale for Depression, the Global Assessment of Functioning Scale, and the Clinical Global Impressions. RESULTS: In the 11 patients who completed the 8-week trial, the mean total CAPS score decreased significantly from baseline (from 82.9 ± 16.1 to 63.5 ± 21.2). The avoidance and hyperarousal subscales showed significant decreases (from 36.2 ± 6.2 to 26.5 ± 9.6 and from 31.9 ± 6.5 to 22.1 ± 7.1, respectively), whereas the re-experiencing subscale remained unchanged. Significant improvements were also noted on all secondary outcome measures. Treatment response was noted within the first 4 weeks of treatment and was maintained throughout the trial. Baclofen therapy was well tolerated, as only 1 patient dropped out due to adverse effects. CONCLUSIONS: Baclofen therapy was effective in treating both the PTSD symptoms and accompanying depression and anxiety in patients with chronic PTSD due to combat. Larger, double-blind, placebo-controlled studies are needed to confirm the efficacy of baclofen in the treatment of PTSD.

Clonazepam for Treatment of Sleep Disturbances Associated with Combat-Related Posttraumatic Stress Disorder

BACKGROUND: Clonazepam is widely used for the treatment of posttraumatic stress disorder (PTSD)—related sleep disturbances despite very limited published data supporting its use for this indication. OBJECTIVE: We conducted a pilot-controlled trial to provide more data on this clinical practice and lay the foundation for more definitive studies. METHODS: The study was designed as a randomized, single-blind (ie, patient only), placebo-controlled, crossover clinical trial involving administration of clonazepam 1 mg at bedtime for one week followed by 2 mg at bedtime for one week. The following week served as a washout period before the alternate treatment was begun. Patients completed sleep diaries each morning upon awakening throughout the study. Parameters included quantity of sleep, quality of sleep, frequency and intensity of difficulty falling or staying asleep, and frequency and intensity of recurrent distressing dreams. RESULTS: Six patients with combat-related PTSD participated in the study. There were no statistically significant differences between clonazepam and placebo for any measure, although clonazepam therapy resulted in mild to moderate numeric improvements in difficulty falling or staying asleep. Adverse effects of clonazepam were generally mild and essentially indiscernible from those attributed to placebo. Only one patient elected to receive further treatment with clonazepam at the conclusion of the trial. CONCLUSIONS: Clonazepam therapy was largely ineffective in improving sleep disturbances, particularly nightmares, associated with combat-related PTSD. The small sample size was a significant limitation of this study, but the prospective design and single-blind, placebo-control parameters were strengths. Further studies are needed to further define the role of this widespread clinical practice.

Pregabalin for the Treatment of Generalized Anxiety Disorder

Objective: To evaluate the efficacy and tolerability of pregabalin in the treatment of generalized anxiety disorder (GAD). Data Sources: A search of PubMed (1966-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) was conducted using the MeSH and free-text terms pregabalin, anxiety disorders, and anxiety. Study Selection and Data Extraction: All English-language articles identified through the search were evaluated for inclusion. Only randomized controlled trials involving the use of pregabalin for the treatment of GAD were included in the review. Data Synthesis: Eight published trials were identified through the search strategy. Successful treatment of GAD with pregabalin versus placebo and active comparators has been reported in clinical trials. Pregabalin lowered total Hamilton Rating Scale for Anxiety scores within 1 week and was effective against both somatic and psychic subcomponents. In 1 controlled clinical trial, pregabalin was found to be effective in patients aged 65 years and older. Another trial demonstrated improved relapse rates when pregabalin, compared with placebo, was used for up to 6 months. The most commonly experienced adverse events were somnolence, dizziness, headache, and dry mouth. Conclusions: Available evidence suggests that pregabalin is effective and well tolerated in the treatment of GAD. As somnolence and dizziness are common adverse effects, caution should be used in elderly patients. Pregabalin rapidly relieves anxiety, a benefit that it may have over many other currently available therapeutic options besides benzodiazepines. While not a first-line therapy in GAD, pregabalin offers another treatment option in patients who do not respond to or who suffer intolerable adverse effects from other agents.

Prazosin for treatment of nightmares related to posttraumatic stress disorder

PURPOSE The efficacy of prazosin for the treatment of posttraumatic stress disorder (PTSD)-related nightmares is reviewed. SUMMARY PTSD is an anxiety disorder that can occur after experiencing or witnessing a life-threatening event, such as military combat, natural disasters, terrorist attacks, serious accidents, or violent personal assaults. The event that induced PTSD is often relived through nightmares or flashbacks. Sleep disturbances affect approximately 70% of patients with PTSD. Several medications have been evaluated for reducing PTSD-related nightmares, with limited success. Prazosin is a centrally and peripherally acting alpha(1)-adrenergic antagonist whose mechanism of action, favorable adverse-effect profile, and low cost make it a promising agent for the treatment of PTSD. To date, two case reports, two chart reviews, three open-label trials, and two placebo-controlled trials have been published documenting the efficacy and safety of prazosin in the treatment of PTSD-related nightmares. Therapy with prazosin resulted in a reduction in nightmares in patients with both combat- and noncombat-related trauma. A therapeutic benefit occurred with prazosin dosages as low as 1 mg daily, and suppression of nightmare symptoms occurred within one week of prazosin initiation. The most frequently reported adverse event was orthostatic hypotension. The variability in the populations studied (e.g., combat, noncombat, recent traumatic experiences) leaves additional unanswered questions that must be addressed in large, randomized, controlled trials. CONCLUSION Prazosin appears to be a promising and well-tolerated agent for the management of PTSD-related nightmares. Further well-designed trials are warranted to establish its place in the treatment of PTSD.

Pharmacotherapy of Eating Disorders

Eating disorders are complex, chronic disorders that are difficult to treat. In addition, the 2 primary eating disorders, anorexia nervosa and bulimia nervosa, may have acute, life-threatening consequences. Medication trials for eating disorders have been hampered by high dropout rates, high placebo response, short trial duration, insufficient doses, and difficult outcome measures. Only 1 medication has been FDA approved for any eating disorder to date, and that is for fluoxetine in the treatment of bulimia. Clearly, new large-scale, independent studies using novel agents, and studying the use of medications for both short- and long-term outcomes, are needed.

The Role of Venlafaxine in the Treatment of Obsessive—Compulsive Disorder

OBJECTIVE: To evaluate the published literature regarding the use of venlafaxine in the treatment of obsessive—compulsive disorder (OCD). DATA SOURCES: MEDLINE (1996–March 2004) and International Pharmaceutical Abstracts (1970–March 2004) were searched using the terms venlafaxine and obsessive—compulsive disorder. A bibliographic search was conducted as well. DATA SYNTHESIS: Successful treatment of OCD with venlafaxine has been reported in case reports, open trials, and blinded trials versus active comparators. The only placebo-controlled trial did not find statistically significant improvement with venlafaxine treatment; however, methodologic limitations may have influenced those results. Venlafaxine appears to be as efficacious as clomipramine, but is preferable to this agent in terms of safety and tolerability. Venlafaxine seems to be similar to paroxetine with respect to both therapeutic effects and adverse effects, but may be inferior to paroxetine when used for nonresponders to previous serotonin-reuptake inhibitor therapy. CONCLUSIONS: Although the relative scarcity of data precludes definitive conclusions, available evidence suggests that venlafaxine is effective and well tolerated in the treatment of OCD. Unfortunately, it has not shown any unique advantages relative to currently available medications.

Are Calcium-Channel Blockers Effective in the Treatment of Tardive Dyskinesia?

Objective To review the data describing the use of calcium-channel blockers in the treatment of tardive dyskinesia (TD). Data Sources A MEDLINE search of the English-language literature and a bibliographic review of pertinent articles examining the use of calcium-channel blockers in the treatment of TD were performed. Medical Subject Headings (MESH) terms used were calcium-channel blockers, tardive dyskinesia, nifedipine, verapamil, and diltiazem. STUDY SELECTION AND DATA EXTRACTION Relevant case reports, open trials, and controlled studies reporting on the efficacy of calcium-channel blockers for treating TD are reviewed. Appropriate conclusions are drawn from the data and guidelines are suggested for the practitioner. Data Synthesis Studies addressing the efficacy of calcium-channel blockers in the palliative treatment of TD have yielded mixed results. Positive findings have been reported for nifedipine, verapamil, and diltiazem; nifedipine may be the most efficacious treatment and diltiazem the least. It appears that patients with TD who can tolerate higher doses of calcium-channel blockers may respond more favorably to treatment. Patient characteristics that may help determine a better response to treatment with calcium-channel blockers include advanced age and more-severe TD. Conclusions To determine the efficacy of calcium-channel blockers in the treatment of TD, additional data are needed from double-blind, placebo-controlled studies with larger sample sizes and longer durations of treatment. Until these data are available, calcium-channel blockers should be considered potentially useful therapy for the heretofore unresponsive TD.

Efficacy of Add-On Topiramate Therapy in Psychiatric Patients with Weight Gain

BACKGROUND: Weight gain is a common adverse effect of many psychotropic medications including antipsychotics, antidepressants, and mood stabilizers. There is a growing body of evidence that topiramate may be useful as an add-on therapy to induce weight loss in patients who have experienced psychotropic-induced weight gain. OBJECTIVE: To determine the efficacy and tolerability of topiramate for treatment of weight gain in a naturalistic mental health clinic setting. METHODS: A retrospective chart review was conducted at a community mental health clinic. Subjects were non-elderly adults who received topiramate therapy beginning in 2002–2005 for documented weight gain during treatment with psychotropic drugs. Primary outcome measures included response rate (based on weight loss of any magnitude) and mean changes in weight and body mass index (BMI). RESULTS: Forty-one patients were included in the study. There was a 58.5% (n = 24) response rate. Mean reductions in weight and BMI were approximately 2.2 kg and 0.5 points, respectively. Responders lost an average of 7.2 kg, whereas nonresponders gained an average of 5.0 kg. Patients with a baseline weight of at least 91 kg and those receiving a greater number of psychotropic medications were more likely to experience success with topiramate therapy. Of the 24 patients who responded to therapy, 22 experienced onset of weight reduction by the next clinic visit (1–4 mo) following either initiation of therapy or titration to the eventual therapeutic dose, and the usual rate of weight loss was 0.45–1.4 kg per month. Therapy was typically initiated at 50 mg/day. The mean maximum dose was 93.9 mg/day and the median maximum dose was 100 mg/day. Seven (17.1%) patients had documented adverse effects to topiramate therapy. CONCLUSIONS: Topiramate therapy resulted in overall modest (ie, <2%) decreases in weight and BMI, but many patients experienced more impressive weight loss. Therapy was generally well tolerated.

Divalproex for the treatment of posttraumatic stress disorder: a retrospective chart review

Objective. Open label trials of divalproex in the treatment of posttraumatic stress disorder (PTSD) show positive results. The objective of this study was to examine the therapeutic effects of divalproex in a larger naturalistic sample of patients with PTSD. Methods. A retrospective analysis was performed on 325 veteran charts identified through a computerized search of PTSD diagnosis matched with pharmacy records (any form of divalproex). The medication names, doses, labs, and dates (except for the divalproex index visit) were blackened. An investigator blinded to the order of visits and blackened information rated the progress notes preceding and following psychopharmacological intervention with divalproex with the Clinical Global Impression Scale for Improvement (CGI-I). Results. Fifty patients met eligibility criteria. Three were treated with divalproex monotherapy and 47 were treated adjunctively. The improved endpoint CGI-I differed significantly from “no change” (P<0.000001). Twenty-five (50%) were rated as very much or much improved on the CGI-I. Patients treated in primary care had a greater improvement compared to those in the mental health setting (P<0.005). Divalproex dosage and serum valproic acid levels (n=37) were well correlated (r = 0.57, P<0.0005). Conclusion. Divalproex treatment improves the global clinical function of veterans with PTSD. Further controlled study is warranted.

Sleep Quality Among Pharmacy Students

Objective. To determine the quality of sleep among pharmacy students in the didactic portion of the curriculum at one school of pharmacy. Methods. The study consisted of an anonymous, voluntary survey that included the Pittsburgh Sleep Quality Index (PSQI), a self-rated instrument that measures sleep habits for a month. Results. The survey was completed by 253 students. Students in the lower grade point average (GPA) category had higher scores on 2 of 7 components of the PSQI and on the global score. Poor sleep quality, indicated by a global PSQI score of greater than 5, was reported by 140 students. The rate of poor sleeping was higher among students in the lower GPA category. Conclusion. Poor sleep quality was pervasive among surveyed pharmacy students in the didactic portion of the pharmacy school curriculum, especially among those with lower GPAs.