Jihad B. Saoud

Responses of “generalized” and “discrete” social phobics during public speaking☆☆☆

Abstract Thirty-six patients meeting DSM-IIIR social phobia criteria (28 “generalized,” 8 “discrete”) and 14 controls were monitored during a 10-minute simulated speech. Both patient groups reported less overall confidence in public speaking than controls. Generalized social phobic patients also exceeded controls in both subjective and manifest anxiety during the simulated speech. Discrete social phobic patients exceeded controls in anticipatory anxiety prior to the speaking challenge and in heart rate prior to and during the challenge. Generalized patients exceeded discrete social phobic patients in lack of confidence in public speaking and in subjective anxiety during the speech, but discrete patients exceeded generalized in heart rate elevation before and during the speech. The results underline the necessity of subtyping social phobia during psychobiological study, and suggest mechanisms by which symptoms are mediated in the two subtypes.

Neuropsychiatric impairment in impulsive personality disorders

It has been suggested that impulsivity and aggression are associated with neuropsychiatric impairment. Neurological soft signs may be a useful marker of nonspecific brain damage, and may therefore be increased in impulsive and aggressive patients compared with normal control subjects. A structured examination was used to evaluate neurological soft signs in 28 patients with personality disorders characterized by impulsivity and 28 healthy control subjects. All of the patients met DSM-III-R criteria for borderline personality disorder, and 10 also met criteria for antisocial personality disorder. All patients were questioned about past history of physical aggression, and a subset of 18 patients underwent neuropsychological testing with a select battery. Left-sided neurological soft signs were significantly increased in patients compared with normal control subjects. Patients with a history of aggression, however, had significantly more right-sided neurological soft signs than those without a history of aggression. Increased neurological soft signs were associated with impairment on the Wisconsin Card Sort, a test of frontal lobe executive function. Specific neuropsychiatric abnormalities, such as lateralized neurological soft signs and associated impairment on select neuropsychological tests, may be present in patients with personality disorders characterized by impulsivity.

Buspirone in social phobia

The novel anxiolytic agent buspirone has been shown to be effective in generalized anxiety disorder, but its utility in phobic disorders is less clear. We examined its efficacy in social phobia in a 12-week open trial. Twenty-one patients who met DSM-III-R criteria for social phobia and who did not respond to 1 week of single-blind placebo were treated with buspirone, and 17 completed a minimum of 2 weeks of treatment. Twelve of these 17 patients met criteria for the generalized subtype of social phobia. At week 12, 8 (47%) of the 17 patients were rated much to very much improved in social phobia symptoms on the Clinical Global Impression Scale. Of the 12 patients who were able to tolerate a dose of 45 mg/day or more, 9 (67%) were at least much improved. Significant improvement was noted on measures of social anxiety and avoidance of social situations. Ratings of generalized anxiety and depression, which were low at baseline, did not change significantly during treatment. The results suggest that buspirone may have modest efficacy in the treatment of social phobia, but confirmation in a placebo-controlled trial is required.

Induction of depersonalization by the serotonin agonist meta-chlorophenylpiperazine.

Sixty-seven subjects, including normal volunteers and patients with obsessive-compulsive disorder, social phobia, and borderline personality disorder, received ratings of depersonalization after double-blind, placebo-controlled challenges with the partial serotonin agonist meta-chlorophenylpiperazine (m-CPP). Challenge with m-CPP induced depersonalization significantly more than did placebo. Subjects who became depersonalized did not differ in age, sex, or diagnosis from those who did not experience depersonalization. There was a significant correlation between the induction of depersonalization and increase in panic, but not nervousness, anxiety, sadness, depression, or drowsiness. This report suggests that serotonergic dysregulation may in part underlie depersonalization.

Timing of neuroendocrine responses and effect of m-CPP and fenfluramine plasma levels in OCD ☆

The present study assesses the timing of and relationship between neuroendocrine response and metabolite blood levels following the partial serotonin (5-HT) agonist m-CPP and the 5-HT releaser/reuptake blocker fenfluramine. Cortisol levels peaked significantly earlier than did prolactin, m-CPP, fenfluramine, or norfenfluramine blood levels by time-to-peak analysis. This earlier cortisol response to both 5-HT agents raises the possibility that peripheral mechanisms may play a role in cortisol release. Since peak m-CPP level correlated even more closely to peak prolactin rise than did peak fenfluramine, this suggests that prolactin response to oral m-CPP challenge is useful in assessing 5-HT function.

A pilot study of biological predictors of treatment outcome in obsessive-compulsive disorder

Although serotonin reuptake blockers such as clomipramine (The Clomipramine Collaborative Study Group 1991) and fluoxetine (Liebowitz et al 1989) are at least partially effective in approximately 60% of patients with obsessive-compulsive disorder (OCD), up to 40% of patients remain refractory. The ability to predict which patients will have a poor response to serotonin (5-HT) reuptake blockers is of clinical interest, as adequate medication trials may involve a minimum of 10-12 weeks, and other alternatives, such as behavior therapy, exist. Some evidence suggests that OCD patients with schizotypal personality (Jenike et al 1986) or with multiple axis II diagnoses (Baer et al 1992) may have a poor response to 5-HT reuptake blockers. In the multicenter clomipramine study, baseline characteristics such as age, gender, duration, severity of OCD, and depression did not correlate significantly with outcome (DeVeaugh-Geiss et al 1990). Phenomenological subtypes of OCD also do not appear to correlate with outcome (Goodman et al 1989). Although some studies fail to show an association between blood levels of clomipramine or desmethylclomipramine and trcatment outcome (Flament et al 1985; Thoren et al 1980), others report that higher clomipramine, but not desmethylclomipramine levels are associated with better outcome (Mavissakalian et al 1990). Other biological variables predictive of treatment outcome have not yet been clearly determined. Selective response of OCD to 5-HT reuptake blockers suggests that serotonin dysfunction may play an important role in this disorder (Zohar and Insel 1987). This hypothesis has been strengthened by pharmacological challenge ~tudies (Zohar et al 1987). We previously reported on the use of the partial 5-HT agonist m-chlorophenyipiperazine (mCPP) to assess 5-HT sensitivity in OCD (Hollander et al 1992). Eleven out of 20 patients (55%) experienced exacerbation of OCD symptoms following mCPP, but none had exacerbations after placebo. Prolactin re-

Alpidem in the treatment of panic disorder.

Alpidem, an imidazopyridine that acts at the gamma-aminobutyric acid/benzodiazepine receptor complex, has been reported to be an effective anxiolytic with a more favorable side effect profile than benzodiazepines. The effect of alpidem was investigated in an 8-week, open, clinical trial in 13 patients with panic disorder, with or without agoraphobia. Three patients were responders (much improved or very much improved), five patients were nonresponders, and five patients dropped out after less than 6 weeks of treatment. Significant improvement was seen in the sample as a whole for spontaneous panic attacks, phobic avoidance, and anticipatory anxiety. Most improvement occurred during the first 4 weeks of treatment, and responders had milder panic disorder at baseline. Adverse effects were generally mild. After 8 weeks of treatment, taper of medication over 2 weeks occurred without significant worsening of panic disorder symptoms. The efficacy of alpidem in the treatment of panic disorder remains uncertain and requires assessment in a controlled trial.

Effects of fenfluramine on plasma homovanillic acid in healthy subjects.

The specificity of fenfluramine as a pharmacological probe of the serotonin system has been questioned, since animal studies with high dose 1-fenfluramine show increases in striatal levels of the dopamine metabolite homo-vanillic acid. To test the specificity of fenfluramine in humans with clinical doses, we compared plasma homovanillic acid (pHVA) concentration in healthy volunteers after administration of fenfluramine (60 mg) and placebo. There were no significant effects on pHVA, which supports previous findings that at doses used in pharmacological challenge paradigms, the effect of fenfluramine on the dopamine system is insufficient to alter measures of its change.