Alprazolam and exposure alone and combined in panic disorder with agoraphobia. A controlled study in London and Toronto.

A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-free follow-up, and a low rate of early placebo drop-outs ('non-evaluables'). The dose of alprazolam was high (5 mg/day). The 154 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trails in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure.

Cerebral pathology in pseudoseizures.

Over a 5-year period 17% of admissions to an epilepsy unit in a psychiatric hospital had pseudoseizures; 42% of these patients also had concurrent epilepsy. Memory deficits were common both in those with pseudoseizures along (50%) and in those with concurrent epilepsy (62%). EEG abnormalities were more common in both groups with pseudoseizures than in a control group of patients with anxiety and affective disorders. Of specific EEG abnormalities only paroxysmal events occurred significantly more frequently in those with concurrent epilepsy than in those with pseudoseizures and in complicated cases of seizure disorder, the presence of cerebral pathology cannot be relied on to distinguish between epileptic and pseudo-seizures.

Obsessive-compulsive beliefs and treatment outcome.

Of 49 compulsive ritualizers one-third perceived their obsessive thoughts as a rational and felt that their rituals warded off some unwanted or feared event (the content of their obsessions). The more bizarre the obsessive belief the more strongly it was defended and 12% of cases made no attempt to resist the urge to ritualize. Neither fixity of belief nor resistance to compulsive urges were related to duration of illness. Patients with bizarre and fixed obsessive beliefs responded as well to treatment (all but three received exposure), as did patients whose obsessions were less bizarre and recognized as senseless. There was no difference in outcome between patients who initially found it hard to control their obsessions or never resisted the urge to ritualize and those who initially could control obsessions or resist rituals. One year after starting treatment, patients whose obsessions and compulsions had improved with treatment recognized their irrationality more readily and controlled their compulsive urges more easily. Beliefs appeared to normalize as a function of habituation.

Relationship of skin conductance activity to clinical features in obsessive-compulsive ritualizers.

Before treatment 49 obsessive-compulsive (o-c) ritualizers were presented with two series of brief stimuli--15,100db tones (brief neutral) and 15 presentations of a ritual-evoking object (brief aversive). Habituation of skin conductance (SC) responses to the tones was reduced compared with that previously found in normal subjects. Neither habituation rates to tones nor aversive stimuli were related to coexisting anxiety or depression or to the severity of o-c symptoms. The increased arousal induced by the aversive stimuli was sustained, that induced by the tones was short-lived and SC level and subjective anxiety had returned to resting levels by the end of the tone series. Concordance between SC activity and subjective anxiety was much greater during and after the presentations of ritual evoking stimuli than of tones. There were few correlations between SC and clinical measures, though patients who strongly resisted and were able to control their compulsive urges were more aroused.

Agoraphobics 5 years after imipramine and exposure. Outcome and predictors.

Five years after treatment in a controlled trial, in which all had received self-exposure homework, a group of 40 agoraphobic outpatients retained marked improvement in agoraphobia, mood, and free-floating anxiety. Frequency of spontaneous panics decreased as much in those who had placebo and self-exposure as in those who received imipramine and self-exposure. Few patients, however, were completely well at 5 years and over half had received further treatment for agoraphobia during the follow-up. Patients who were still highly phobic at the end of the clinical trial were more often prescribed psychotropic medication during follow-up and remained phobic at 5 years. Phobic improvement had generalized more in those patients with very low than in those with moderate pretreatment Hamilton depression scores. Frequency of initial spontaneous panics did not predict outcome. Improvement in agoraphobia was associated with improved marital adjustment. Those who began with the best marital, work, and social adjustment were more improved in their phobias 5 years later.

Anorgasmia from clomipramine in obsessive-compulsive disorder. A controlled trial.

Forty-six patients with obsessive-compulsive disorder undergoing a double-blind controlled study of clomipramine and placebo were interviewed to assess changes in sexual function. Of 33 patients with previously normal organism, nearly all of the 24 on clomipramine developed total or partial anorgasmia; none of the 9 on placebo did so. Anorgasmia persisted with minimal tolerance over the five months that clomipramine was taken. Men and women were equally affected. Sexual side-effects are easily missed without a structured interview, and can detract from the value of drug treatment.

Drug treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is an uncommon but difficult to manage problem. Behaviour therapy is the treatment of choice, with clomipramine as an adjunct in patients with coexisting depression. However, the incidence of side effects with the doses required (up to 200 mg daily, or occasionally higher) is high, and the side effects may be intolerable to some patients. Benzodiazepines have no effect on the core symptoms of OCD, and their usefulness as long term anxiolytics is outweighed by the risks of physical and psychological dependence. There is no place for antipsychotic drugs in managing obsessive-compulsive disorder.