Faculty Bibliography

BACKGROUND: Nearly one third of patients suffering from schizophrenia do not fully respond to antipsychotic medication. Safe, effective, and cost-efficient methods to reduce symptoms are clearly needed; therefore, lithium as an adjunct to fluphenazine decanoate was tested in a placebo-controlled trial in outpatients who were part of the Treatment Strategies of Schizophrenia (TSS) study. METHOD: Forty-one patients with DSM-III schizophrenia or schizoaffective disorder were assigned to either adjunctive lithium or placebo after at least 6 months of fluphenazine decanoate treatment to stabilize symptoms had failed. The trial was designed for 8 weeks of treatment, and patients assigned to placebo could afterward be administered lithium in an 8-week, open-label study. RESULTS: Assessment of the intent-to-treat analysis revealed no significant differences in demographic variables between the lithium and placebo groups. Although both groups showed significant (p = .00135) improvement as measured by total scores on the Brief Psychiatric Rating Scale (BPRS), there were no significant differences in response between the lithium and placebo groups. Patients originally treated with placebo added to neuroleptic did not have significantly greater improvement when receiving open-label adjunctive lithium. CONCLUSION: Although success with lithium augmentation therapy for persistent psychosis has been reported in the past, this study of well-characterized patients showed no benefit for this common strategy, thus indicating that care be used in utilizing lithium augmentation.

The functional anatomy of anxiety involves amygdala-based neurocircuits with critical reciprocal connections to the medial prefrontal cortex. Traumatic experiences leave emotional imprints involving the amygdala, with facilitated fear-conditioned associations involving declarative memory traces. Avoidance conditioning is an additional component. An understanding of the functional anatomy of anxiety allows for a new perspective on the various anxiety disorders. The neurotransmitters involved in these circuits are reviewed for their relevance to the pharmacologic choices in the treatment of anxiety. Potent serotonin reuptake inhibitors appear to have superior efficacy in many of the anxiety disorders, with indications that norepinephrine reuptake inhibitors have an advantage in severe forms of major depression. Medications with dual effects--blocking reuptake of both serotonin and norepinephrine (e.g., clomipramine and venlafaxine XR)--have superior benefits in achieving remission in major depression and GAD. These medications may also offer a faster onset of action and theoretically superior benefits in patients with comorbid anxiety disorder and major depression.

This article reports the preliminary findings of a two-phase trial examining the efficacy of venlafaxine in trichotillomania. Phase 1 is a 12-week, open-label, prospective trial of venlafaxine in trichotillomania. Venlafaxine was effective in significantly reducing the symptoms of trichotillomania; 8 of 12 patients were considered responders. The implications of the efficacy of venlafaxine in trichotillomania are discussed, including its important advantages over other available antidepressant and anxiolytic medications.

BACKGROUND: Previous studies have examined dose reduction and family treatment in schizophrenia, but none has examined their interaction. This study assessed the impact of dose reduction of antipsychotic medication and family treatment on relapse and rehospitalization during maintenance treatment. METHODS: Subjects were 313 male and female outpatients at 5 centers with a DSM-III-R diagnosis of schizophrenia or schizoaffective disorder. In a 3 x 2 design, subjects were randomized to 1 of 3 medication strategies using fluphenazine decanoate under double-blind conditions: continuous moderate dose (standard) (12.5-50 mg every 2 weeks); continuous low dose (2.5-10 mg every 2 weeks); or targeted, early intervention (fluphenazine only when symptomatic). Subjects also were randomized to 1 of 2 family treatment strategies (supportive or applied). Supportive family management involved monthly group meetings. The more intensive applied family management involved monthly group meetings and home visits where communication and problem-solving skills were taught. Patients and families were treated and assessed for 2 years. RESULTS: Both continuous low-dose and targeted treatment increased use of rescue medication and relapse; only targeted treatment increased rehospitalization. This pattern was consistent across both family treatments; there were no differences between family treatments. CONCLUSIONS: These findings reaffirm the value of antipsychotic medication in preventing relapse and rehospitalization. The absence of family treatment differences may be because both conditions engaged families.

Assessment of treatment response in panic disorder is complicated by the multidimensional aspects of panic disorder and agoraphobia, the short-term benefits from nonspecific aspects of treatment, and placebo response. Response to treatment with psychological and pharmacologic treatments of panic disorder is reviewed in this context. The experience of several Phase III studies of fluvoxamine in the treatment of panic disorder is examined as an illustrative example. When the response to placebo or comparison treatment in a study is high, no conclusion can be drawn about the true efficacy of the active treatment.

Posttraumatic stress disorder (PTSD) is a significant problem following rape, yet reports on the efficacy of pharmacological agents in this population are lacking. The results of an open 12-week clinical trial utilizing sertraline (mean dose 105 mg) in the treatment of adult female rape victims with chronic PTSD are presented. The five completers were, on average, 41.6 years old and 15.6 years postassault. Sertraline reduced PTSD and related symptoms in these rape victims. The mean Clinician Administered PTSD Scale (CAPS) scores decreased by 53%, with four out of five participants responding positively to treatment. These preliminary results support the need for systematic assessment of sertraline in this population.

Major depressive disorder (MDD) is a common affective disorder that is associated with a range of psychiatric disturbances. The pathophysiology of MDD is commonly believed to involve the reduced availability of the monoamines, serotonin (5-HT) and norepinephrine (NE), the enhancement of which is also believed to mediate, at least in part, the therapeutic effects of antidepressants. The first-generation antidepressants, the tricyclic antidepressants (TCAs), provide considerable efficacy but have several limitations, including (1) delayed onset of action, (2) intolerable or distressing side effects, (3) low therapeutic index, and (4) a significant proportion of nonresponders. The second-generation antidepressants, the selective-serotonin-reuptake inhibitors (SSRIs), mitigate some of the side effects associated with the TCAs by selectively inhibiting the reuptake of 5-HT. Venlafaxine is a new antidepressant that blocks reuptake of both 5-HT and NE. It, like the SSRIs, has a relatively benign side-effect profile. In addition, it may exert a rapid onset of action, and it appears to be particularly effective in moderate-to-severe depression and in patients who have treatment-refractory depression.

Trichotillomania is a disorder characterized by hair-pulling and resulting hair loss. Hair is usually pulled from the scalp, eyelashes, eyebrows, beard, and pubic area. Sufferers often resort to wearing wigs or elaborate hair styles and make-up to camouflage bald patches. It occurs more frequently in women and is associated with considerable distress. The two treatments of choice currently are pharmacotherapy and cognitive-behavioral therapy. The choice of assessment procedures includes self-monitoring, saving hairs, interview, observational rating, digital photograph and computer scoring, significant others' report, and standardized measures. Goals of assessment in trichotillomania and advantages and disadvantages of assessment procedures are discussed. The Trichotillomania Diagnostic Interview is presented as a standardized diagnostic interview.