Long-Term Treatment of Posttraumatic Stress Disorder

Rothbaum and colleagues¹¹ studied augmentation of sertraline(Drug information on sertraline) with PE. Patients with PTSD were treated with sertraline for 10 weeks and then randomly selected to receive an additional 5 weeks of sertraline for a total of 15 weeks of treatment. Patients who had at least a 20% reduction in PTSD symptom severity were assigned to the second phase of the study. These patients were treated with sertraline alone (n = 31) or sertraline plus PE twice weekly (n = 34). Most of the participants were women (85%) who had suffered non- combat-related trauma including sexual and nonsexual assault, death of a close relative or friend, motor vehicle accident, or other trauma. Outcome measures using the Structured Interview for PTSD showed that sertraline treatment during the first 10 weeks resulted in a significant reduction in symptom severity, but there was no change in symptom severity after an additional 5 weeks of sertraline treatment (Table 2). In contrast, the patients who received PE augmentation had a further reduction in symptoms. This occurred only in patients who originally had a partial response to sertraline.

Another study investigating long-term maintenance of PTSD with psychotherapy compared short-term and long-term efficacy of fluoxetine(Drug information on fluoxetine), psychotherapy (eye movement desensitization and reprocessing [EMDR]), and placebo.¹² Eighty-eight participants were randomly assigned to receive fluoxetine, EMDR, or placebo over an 8-week treatment phase. They were blindly assessed after an additional 6 months of treatment using the CAPS as the primary outcome variable. EMDR was more effective than fluoxetine or placebo in adult-onset trauma victims at 6-month follow-up. This compared with a 33% reduction in patients with childhood-onset trauma who received EMDR. There was also symptom reduction in the patients with adult-onset trauma who received fluoxetine.

An earlier study investigated the ability of CBT to prevent the development of chronic PTSD in civilian trauma victims.¹³ The types of trauma included nonsexual assault and motor vehicle accidents. Most patients at baseline met criteria for acute stress disorder. The investigators assessed 45 patients who were given 5 sessions of PE (n = 14), combined PE and anxiety management (n = 15), or supportive therapy (n = 16). Forty-one patients were assessed at a 6-month follow-up appointment. There was a reduction in the number of patients meeting diagnostic criteria for PTSD in those who had received PE (2 out of 14), and PE plus anxiety management (3 out of 15) compared with supportive therapy alone (10 out of 15) at the 6-month assessment. This study supports the notion that early intervention with CBT, and in particular PE, may mitigate the long-term effects of trauma.

Case reports and small open trials support the notion that γ-aminobutyric acid (GABA) mechanisms may be involved in PTSD. However, only one published study has addressed long-term treatment with an anticonvulsant agent, tiagabine(Drug information on tiagabine), which is a selective GABA reuptake inhibitor. A 12-week open-label trial was conducted in 29 patients with PTSD.¹⁴ Treatment responders were randomized to double-blind, placebo-controlled treatment. In the 19 patients who completed open-label treatment, significant improvement (P < .05) was seen in all outcome measures; 18 patients with at least minimal improvement were entered into the 24-week randomized phase. The mean dosage of tiagabine at the end of the randomized phase was 10.8 mg daily. The group treated with tiagabine was more likely to achieve remission than the placebo group (P < .08). There was no difference in relapse rates between groups. Tiagabine was well tolerated. The authors noted that larger controlled trials are needed for GABAergic agents including tiagabine in PTSD.

Acute studies have supported a possible role for atypical antipsychotics, in particular for treatment-refractory PTSD or in patients with comorbid psychosis. A restrospective review of childhood trauma victims (n = 6) with chronic PTSD and psychotic symptoms suggested that clozapine was effective in reducing psychiatric symptoms in 4 of 6 of the adolescents during a 6-month treatment period.¹⁵ Five of the patients also had a reduction in psychotic (hallucinatory) symptoms.

One long-term study of risperidone(Drug information on risperidone) for combat-related chronic PTSD was conducted by Bartzokis and colleagues.¹⁶ This was a single-site, double-blind, placebo-controlled trial (n = 73) that included a 5-week residential phase and a 3-month outpatient follow-up phase. The primary outcome measure was the CAPS score with a number of secondary efficacy and safety measures. Sixty-five patients were randomized and 48 completed the study. There was significant improvement in patients treated with risperidone versus the placebo group on the total CAPS scores and also on the CAPS hyperarousal subscale scores. Most patients were titrated to 3 mg of risperidone daily with 2 patients receiving 2 mg. Risperidone was well-tolerated. This was an adjunctive study with other medications held constant.

Although early acute studies with antiadrenergics, in particular the α₁-antagonist prazosin(Drug information on prazosin), have been promising. To this author's knowledge there have been no long-term studies with these or other agents such as the benzodiazepines or buspirone(Drug information on buspirone). Raskind and colleagues¹⁷ studied prazosin in a 20-week, double-blind, crossover study that was promising in demonstrating a reduction in sleep disturbances and other PTSD symptoms; however, actual active treatment time was 10 weeks.

Long-term studies, in particular with antidepressants or antidepressants combined with psychotherapy, show promise in the continuation and maintenance phases of treatment for chronic PTSD. It is evident from both acute and long-term studies that although PTSD may respond to a variety of treatment interventions, at the end of the trials many patients still have significant symptom burden.¹⁸ More studies are needed to investigate combination medication and psychosocial treatment interventions. Moreover, there are limited data on the effectiveness of other classes of psychotropics, especially for continuation or maintenance treatment. At this point, it is reasonable to continue to give patients with chronic PTSD an SSRI or SNRI antidepressant if they have responded to acute-phase treatment. Ideally, the antidepressant should be combined with some form of CBT.