Peter Tyrer

BENZODIAZEPINE WITHDRAWAL SYMPTOMS AND PROPRANOLOL

40 patients seen in general practice and psychiatric outpatient clinics who had taken lorazepam or diazepam alone in regular dosage for a mean period of 3.6 years had their benzodiazepine replaced by propranolol (60--120 mg/day) or placebo for two weeks under double-blind conditions. Depending on the criteria for the definition of an abstinence syndrome, 27--45% of the patients had withdrawal symptoms during the study. Propranolol did not affect the drop-out rate or the incidence of withdrawal symptoms but significantly reduced their severity in patients completing the study. The percentage fall in serum levels of desmethyldiazepam in patients who experienced withdrawal symptoms after stopping diazepam was significantly greater in patients with no withdrawal symptoms.

GRADUAL WITHDRAWAL OF DIAZEPAM AFTER LONG-TERM THERAPY

41 outpatients who were long-term consumers of diazepam in therapeutic dosage were gradually withdrawn from the drug over 3 months by stepwise reduction. In a double-blind procedure half the patients began withdrawal immediately and half after 8 weeks. Of 36 patients who completed treatment, 16 (44.4%) experienced true withdrawal phenomena on reducing their drugs, but 8 other patients had pseudo-withdrawal reactions at a time when their drug treatment was unchanged. The pseudo-withdrawal reactions consisted of an increase in anxiety symptoms only, whereas true withdrawal symptoms also included perceptual changes and psychotic symptoms. Examination of pharmacological and clinical predictors of withdrawal phenomena and later relapse showed that personality factors were the most important, patients with passive-dependent traits having a significantly greater prevalence of withdrawal reactions.

THE NOTTINGHAM STUDY OF NEUROTIC DISORDER: COMPARISON OF DRUG AND PSYCHOLOGICAL TREATMENTS

210 psychiatric outpatients with generalised anxiety disorder (71), or panic disorder (74), or dysthymic disorder (65) diagnosed by an interview schedule for DSM-III were allocated by constrained randomisation to one of five treatments: diazepam (28), dothiepin (28), placebo (28), cognitive and behaviour therapy (84), and a self-help treatment programme (42). All treatments were given for 6 weeks and then withdrawn by 10 weeks. Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2, 4, 6, and 10 weeks after randomisation. 18 patients had insufficient data for analysis because of early drop-out. There were no important differences in treatment response between the diagnostic groups, but diazepam was less effective than dothiepin, cognitive and behaviour therapy, or self-help, these three treatments being of similar efficacy. Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period, and those allocated to dothiepin and cognitive and behaviour therapy took the least.

Personality, functioning and symptomatology.

A random sample of 200 people selected from urban and rural communities was assessed using structured interview schedules to measure the prevalence of personality disorder and psychiatric illness and their relation to social functioning. Explosive personality disorder was the most prevalent type of abnormal personality. Social functioning was significantly worse in those with personality disorder than those with normal personality but there was no difference between the various diagnostic categories of abnormal personality. Social functioning differed between some PSE diagnostic categories. An assessment was made of the variables contributing to mean social functioning score, of the interactions between them, and of the correlation between social functioning symptomatology.

The diagnostic status of patients with conspicuous psychiatric morbidity in primary care.

A 7% one-year prevalence rate of conspicuous psychiatric morbidity was found in patients attending a single general practice. The nature of the morbidity was examined by a detailed assessment of mental state and personality, using interview schedules administered by a psychiatrist. Depressive disorders were presented by nearly half of the patients. The overall sex incidence of the disorders was equal, but alcohol abuse was more common in males. A personality disorder was present in 33.9% of all patients seen, although it was rarely diagnosed as the primary problem and was linked to the diagnosis of anxiety states, rather than depressive neurosis. These findings are discussed in relation to other epidemiological studies in primary care.

The Nottingham Study of Neurotic Disorder: relationship between personality status and symptoms

Two hundred and ten psychiatric patients with one of three DSM-III diagnoses, generalized anxiety disorder (N = 71), panic disorder (N = 74) or dysthymic disorder (N = 65), were included in a clinical trial in which diazepam, dothiepin or placebo tablets, cognitive and behaviour therapy, or a self-help package were given over ten weeks. Personality status was assessed independently using a structured interview, the Personality Assessment Schedule. One hundred and ninety-eight patients had personality assessments, 89% with a close informant. Thirty-six per cent had a personality disorder and these patients had more severe psychopathology than those with no personality disorder. Personality disorder was more common in patients with dysthymic disorder and this group responded less well to treatment. The category of personality disorder had no apparent influence on symptoms.

Monoamine oxidase inhibitors in anxiety disorders

Monoamine oxidase inhibitors (MAOIs) have been shown to be significantly superior to placebo in the treatment of some anxiety disorders, particularly agoraphobia and mixed anxiety--depressive states. There is no convincing evidence that MAOIs are effective treatment in pure anxiety states, whether or not panic is present as a major symptom, although they are effective in so-called endogenous anxiety. Many past published studies of MAOIs have yielded poor results because the drugs have been prescribed for insufficient time (less than four weeks) or at too low dosage. There are no important therapeutic differences between the MAOIs apart from the faster speed of response with the nonhydrazine compound, tranylcypromine. Treatment often has to be long-term, and some degree of pharmacological dependence may develop. A few clinical studies have compared the efficacy of MAOIs and tricyclic antidepressants in anxious disorders. There is growing evidence that MAOIs are somewhat more effective than tricyclic antidepressants in the treatment of anxiety disorders and when phobic anxiety is an important component of a depressive disorder.

Schizophrenia: no longer a functional psychosis

Abstract Accumulating evidence from the last ten years has demonstrated that schizophrenia can no longer be regarded as a functional psychosis but an organic one. Many studies have demonstrated ventricular enlargement in schizophrenia using CT scans, and precise neuroanatomical evidence of brain changes in schizophrenia have now been demonstrated by Crow and his colleagues. The brains of patients with schizophrenia were found to be lighter than those of patients with primary affective disorder; they were also found to have enlarged lateral ventricles, particularly in the temporal horn, and to have significantly thinner parahippocampal cortices. These findings are consistent with abnormalities in neuropeptide concentrations in the temporal lobe (particularly in the amygdala) of schizophrenic patients, and suggests that schizophrenia is a temporal lobe syndrome. Its cause remains elusive but viral infection could be responsible.

Changes in human whole blood 5-hydroxytryptamine (5-HT) and platelet 5-HT uptake during treatment with paroxetine, a selective 5-HT uptake inhibitor:

The effects of the specific 5-hydroxytryptamine (5-HT) reuptake inhibitor parox etine on whole blood 5-HT and the uptake of 3H-5-HT by platelets was determined in 17 patients with resistant depression. The biochemical parameters were measured before paroxetine treatment, during treatment and after withdrawal of treatment. Two of the 17 subjects failed to complete the trial; of the remaining subjects 12 showed a marked decrease in whole blood 5-HT and 3H-5-HT uptake into platelets. The remaining three patients showed a variable response both in terms of whole blood 5-HT and platelet uptake during paroxetine treatment. At the end of treatment blood 5-HT tended to return towards normal although this was delayed. There was no significant correlation between the change in blood 5-HT and Hamilton score during paroxetine treatment. The results confirm that inhibition of 5-HT uptake mech anisms are associated with decreased whole blood 5-HT but that changes in whole blood 5- HT do not necessarily reflect the clinical efficacy of 5-HT uptake blocking drugs in the treatment of depression.

Clinical effects of abrupt withdrawal from tri-cyclic antidepressants and monoamine oxidase inhibitors after long-term treatment

51 psychiatric outpatients with depressive, anxiety and phobic neuroses were withdrawn from their maintenance treatment with tricyclic antidepressant drugs or the monoamine oxidase inhibitor, phenelzine, at a time mutually agreed between patient and doctor. Self-ratings of anxiety and depression were recorded at the time of withdrawal and at weekly intervals thereafter for 4 weeks. An increase in symptoms after withdrawal was found to be more likely after longer duration of maintenance treatment and in patients taking phenelzine.