Treatment of posttraumatic stress disorder by exposure and/or cognitive restructuring: a controlled study.

BACKGROUND: Unanswered questions from controlled studies of posttraumatic stress disorder concern the value of cognitive restructuring alone without prolonged exposure therapy and whether its combination with prolonged exposure is enhancing. METHODS: In a controlled study, 87 patients with posttraumatic stress disorder of at least 6 months' duration were randomly assigned to have 10 sessions of 1 of 4 treatments: prolonged exposure (imaginal and live) alone; cognitive restructuring alone; combined prolonged exposure and cognitive restructuring; or relaxation without prolonged exposure or cognitive restructuring. RESULTS: Integrity of audiotaped treatment sessions was satisfactory when rated by an assessor unaware of the treatment assignment. Seventy-seven patients completed treatment. The pattern of results was similar regardless of rater, statistical method, measure, occasion, and therapist. Exposure and cognitive restructuring, singly or combined, improved posttraumatic stress disorder markedly on a broad front. Gains continued to 6-month follow-up and were significantly greater than the moderate improvement from relaxation. CONCLUSION: Both prolonged exposure and cognitive restructuring were each therapeutic on their own, were not mutually enhancing when combined, and were each superior to relaxation.

Six-year follow-up after exposure and clomipramine therapy for obsessive compulsive disorder.

To determine whether gains from exposure therapy are lasting in patients with chronic obsessive compulsive disorder, the authors followed up 34 (85%) of 40 such patients who had been treated 6 years earlier with exposure therapy for 3 or 6 weeks and with clomipramine or placebo for 36 weeks. Severity of obsessive compulsive disorder was assessed by rating the discomfort caused by the time devoted to four target rituals, the Behavioral Avoidance Test, and the Compulsion Checklist. Mood was assessed by the 17-item Hamilton Rating Scale for Depression, the Wakefield Self-Assessment Depression Inventory, and the Anxiety scale. In addition, the patients' general adjustment was assessed. The authors found that the group as a whole remained significantly improved on obsessive compulsive symptoms, work and social adjustment, and depression; however, the group returned to pretreatment levels (slight to moderate) of general anxiety. They found that neither clomipramine nor placebo affected long-term outcome and that the majority of patients who were taking clomipramine or other antidepressants at follow-up were no more improved that those who were not taking antidepressants. Better long-term outcome correlated with more exposure therapy (6 weeks of therapy vs. 3 weeks) and with better compliance with the exposure therapy homework. The best predictor of long-term outcome was improvement at the end of treatment. Subjects who had initially been most depressed were more likely to receive psychotropic medication during follow-up. Initial severity of illness did not preclude benefit from exposure therapy.

Pre-treatment predictors of treatment outcome in panic disorder and agoraphobia treated with alprazolam and exposure.

Pre-treatment predictors of treatment outcome were examined in a group of 144 patients with panic disorder and agoraphobia randomly allocated to alprazolam+exposure (AE), placebo+exposure (PE), alprazolam+relaxation (AR), and placebo+relaxation (PR). First-time psychotropic medication use, severity of agoraphobic disability, and longer duration of illness predicted less global improvement at post-treatment. Pre-treatment severity of agoraphobia predicted less improvement both in the short- and the long-term. Predictors of poorer outcome at 6-month follow-up were older age, past history of depression, severity of phobia targets, and longer duration of illness. Sex, source of referral, pre-treatment depression-anxiety-panic, and expectancy from treatment did not relate to outcome.

Alprazolam withdrawal symptoms in agoraphobia with panic disorder: observations from a controlled Anglo-Canadian study.

The study examines the effect of discontinuing alprazolam in panic disorder+agoraphobia patients. Fifty-seven alprazolam and 50 placebo agoraphobia+panic disorder patients, who had participated in an 8 week double- blind controlled study of alprazolam at average doses of 5 mg daily, were withdrawn gradually from their medication over the subsequent 8 weeks. The effects of discontinuation of medication on anxiety, panic, depression, phobia and withdrawal symptoms were examined during the taper phase and over the following 6 months. Alprazolam patients deteriorated on anxiety, panics, Hamilton depression and phobia. There was no difference between the two drug groups on rebound. Serious withdrawal symptoms did not arise, but weight loss, sweating and muscle twitching were more common in alprazolam patients. The deterioration in alprazolam patients persisted up to 6 months post-taper. A high dose of alprazolam at week 8 was the best predictor of subsequent deterioration. Discontinuation of alprazolam leads to recurrence of the original disorder in some patients. Rebound and severe withdrawal reactions were not found during gradual taper of alprazolam, but minor withdrawal symptoms did arise. The study shows the importance of using gradual taper to minimize withdrawal effects.

Urinary cortisol during exposure in obsessive-compulsive ritualizers.

Nineteen obsessive-compulsive (OC) ritualizers were exposed to both brief and prolonged neutral and aversive stimuli (the latter evoked a significant urge to ritualize). Urinary cortisol and subjective anxiety were measured over 3 1/2 hours throughout the experiment, and cortisol secretion was compared to a control session the previous day. Both groups showed higher cortisol secretion after exposure compared to the control session. Only the group that received prolonged aversive stimuli, in addition to brief aversive and neutral stimuli, showed significantly higher urinary cortisol levels after the session. Cortisol response correlated with subjective anxiety reports during prolonged aversive stimulation only.

Agoraphobia and panic disorder: 3.5 years after alprazolam and/or exposure treatment.

BACKGROUND: Long-term follow-ups after controlled studies of exposure therapy for agoraphobia/panic are few. Most of these studies found that improvement during treatment persists to the end of follow-up. METHODS: Out of 69 patients with panic disorder plus agoraphobia who had been in an 8-week controlled study of alprazolam and/or exposure, 31 were followed up at a mean of 3.5 years later (4 years after trial entry). The 31 patients followed up included more cases who had relapsed at week 43 than did the group which did not attend the 3.5-year follow-up. RESULTS: As a group, followed-up cases maintained their gains over the 3.5 years, more so among ex-exposure than ex-relaxation cases. Ex-exposure patients did significantly better than relaxation patients on disability and survival time. Ex-alprazolam and ex-exposure patients did not differ significantly on any variable at the 3.5-year follow-up. No baseline variable predicted outcome at follow-up. CONCLUSIONS: Present results modestly confirm those of previous studies finding lasting improvement years after exposure, though some residual symptoms were the norm.

Gender-divergent aetiological factors in obsessive-compulsive disorder.

Among 307 adults with OCD, early onset (age 5-15 years) was more common in men and later onset (age 26-35 years) in women. Early onset was associated with more checking, and late onset with more washing. More women than men had a history of treated depression; 12% of the women but none of the men had a history of anorexia. More women than men were married. Gender-divergent features may reflect differential aetiological factors. Our sample resembled others in the literature in its slight overall female preponderance, low rate of marriage and low fertility, onset mainly before age 35 years, chronicity, and common present and past depression.

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.

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.

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.

Does exposure to internal cues enhance exposure to external cues in agoraphobia with panic? A pilot controlled study of self-exposure.

BACKGROUND: The value of internal (interoceptive) cues for exposure is under debate and so was tested in a pilot controlled study. METHODS: Outpatients with panic disorder and severe agoraphobia were randomised to 10 weeks of self-exposure to either (1) both internal (interoceptive) and external cues (n = 12) or (2) external cues only (n = 14). Both groups were trained in slow deep breathing and asked to carry out daily self-exposure homework. Neither group had cognitive restructuring. RESULTS: By post-treatment and follow-up all outcome measures improved significantly in both treatment groups. The two groups did not differ significantly in outcome, though slightly more patients who had exposure to both internal and external cues improved 50% or more on phobic avoidance and fear. CONCLUSIONS: A larger controlled study is now worthwhile to tell if such small differences can be significant.

Should treatment distinguish anxiogenic from anxiolytic obsessive-compulsive ruminations? Results of a pilot controlled study and of a clinical audit.

In a small pilot controlled study over 8 weeks, 12 obsessive-compulsive ruminators listened for 2 h daily to their own audiotaped voice either (1) describing their anxiogenic thoughts (exposure) but omitting anxiolytic thoughts (mental/cognitive rituals), or (2) reading neutral prose or poetry. Taking all patients, both groups improved similarly. However, exposure patients who became anxious early in exposure slightly more improved. Consistent with this, in a clinical audit of 57 ruminators treated by trainee clinicians over 12 years, outcome improved significantly once practice changed so that exposure only involved anxiogenic thoughts, not anxiolytic thoughts, the latter being stopped.

Long-term effects of alprazolam on memory: a 3.5 year follow-up of agoraphobia/panic patients.

BACKGROUND: Benzodiazepines (BZs) can impair explicit memory after a single dose and also when taken repeatedly for treatment of anxiety disorders. A previous study with agoraphobia/panic patients found that the BZ alprazolam impaired memory during an 8-week treatment and residual impairments were still manifest several weeks after drug withdrawal (Curran et al. 1994). The present study followed up the same group of patients 3.5 years after treatment to determine whether those memory impairments persisted. METHOD: Thirty-one patients, 15 who had originally been treated with alprazolam and 16 with placebo, were assessed on a battery of psychometric tests and self-rating scales. RESULTS: Ex-alprazolam patients performed at the same levels as ex-placebo patients on the memory task and on other objective tests. Performance levels of both groups were similar to pre-treatment baselines, however there were differences in subjective ratings whereby ex-alprazolam patients rated themselves as less attentive and clear headed and more incompetent and clumsy than ex-placebo patients. CONCLUSIONS: Explicit memory impairments found while patients were taking alprazolam and weeks after drug withdrawal did not persist 3.5 years later. We suggest that the memory impairments observed in our previous study weeks after withdrawal of alprazolam were not residual effects of alprazolam but rather were due to the drug's interference with practice effects on the tests and habituation of anxiety over repeated exposure to the test situation.

Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder.

BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.

Beliefs, sense of control and treatment outcome in post-traumatic stress disorder.

BACKGROUND: Few studies have shown that maladaptive beliefs relate to treatment outcome. METHOD: In a randomized controlled study, 87 patients with post-traumatic stress disorder (PTSD) had exposure therapy alone or cognitive restructuring alone, or both combined, or relaxation. Independent blind assessors assessed patients at pre-, mid- and post-treatment and at follow-up; at those times patients rated cognitive, behavioural and emotional aspects of their disorder. RESULTS: Baseline beliefs about mistrust, helplessness, meaninglessness and unjustness of the world related to baseline PTSD symptoms but did not predict treatment outcome, though improvement in certain beliefs correlated with more symptom improvement. Several 'key' beliefs changed after, and none before, symptoms improved. At post-treatment, sense of control and attribution of gains to personal efforts predicted maintenance of gains at follow-up. CONCLUSIONS: Baseline beliefs and improvement in beliefs did not predict outcome. Post-treatment sense of control/internal attribution predicted maintenance of gains at follow-up. How much sense of control is produced by or causes improvement deserves testing.

Clomipramine, self-exposure and therapist-aided exposure for obsessive-compulsive rituals.

A randomised treatment design for 49 chronically obsessive-compulsive ritualising patients was devised and three controlled comparisons were made. 1. During 7 weeks of self-exposure instructions, clomipramine treatment improved some measures of rituals and depression significantly more than did placebo medication; this effect was transient and disappeared as drug treatment and exposure were continued for a further 15 weeks. 2. During 11-16 weeks of clomipramine treatment, self-exposure instructions yielded highly significantly more patient improvement than did anti-exposure instructions on nearly all measures of rituals and some of social adjustment. 3. Adding therapist-aided exposure (1.3 hours) to self-exposure instructions (3 hours) after 8 weeks had a barely significant transient effect of dubious clinical value, which was lost by the end of exposure (at week 23) and during follow-up assessments to week 52. We conclude that of the three therapeutic factors tested, self-exposure was the most potent; clomipramine played a limited adjuvant role, and therapist-aided exposure a marginal one.

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.

Relationship of panic, anticipatory anxiety, agoraphobia and global improvement in panic disorder with agoraphobia treated with alprazolam and exposure.

In a controlled trial of alprazolam and exposure in 154 patients with panic disorder with agoraphobia, relations between panic, anticipatory anxiety, and phobic avoidance were examined. The three symptoms were independent of one another at baseline and improved largely independently during treatment; only early improvement in avoidance predicted global improvement after treatment. Global improvement was more related to reduction of avoidance than a decrease in panics. Panic was not a valuable outcome measure in panic disorder with agoraphobia.

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.