Nicholas Seivewright

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 All treatments were given for 6 weeks and then withdrawn by 10 weeks.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.

The general neurotic syndrome: a coaxial diagnosis of anxiety, depression and personality disorder

The validity of the general neurotic syndrome, a combination of anxiety, depression and dependent personality disorder, was examined in a 2‐year study of outpatients with dysthymic, panic and generalized anxiety disorder diagnosed using a structured interview schedule. The general neurotic syndrome, found in a third of the patients, was associated with greater mental disorder and a significantly worse outcome than patients without the syndrome. It did not, however, predict response to treatment. Further analysis revealed that the general neurotic syndrome was a better predictor of short‐ and long‐term outcome than any other variable apart from initial psychopathology score. It is argued that the syndrome may represent a personality diathesis that makes the individual more vulnerable to both anxiety and depressive symptoms.

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.

A three-year follow-up of psychiatric morbidity in urban and rural primary care.

Follow-up by examination of medical and psychiatric records was carried out on 357 patients with conspicuous psychiatric morbidity in two general practices three years after clinical and personality assessment using structured interview schedules. One practice was an inner-city urban one and the other was rural. Full follow-up data over the 3-year period was available for 301 patients (84.3%). After three years patients with personality disorder and those in the urban practice had greater morbidity, more contacts with all levels of the psychiatric service and more psychotropic drugs, particularly benzodiazepines. Despite this increased morbidity, the number of consultations with the general practitioner for psychiatric illness was no higher in the urban group and those for medical illness were significantly higher in the rural one. The implications of the findings are discussed with particular reference to developments in community psychiatric care.

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.

Longitudinal study of the influence of life events and personality status on diagnostic change in three neurotic disorders

It has been known for many years that diagnosis within the neurotic spectrum of disorders is temporally unstable and also that life events can be major precipitants of change in symptoms. Reasons for this instability could include inherent inadequacy of current diagnostic practice, the influence of life events as an agent of diagnostic shift, and an innate course of disorder with features dependent on the stage at which disorder presents (e.g., development of panic to agoraphobia). These possibilities were examined in a prospective study that was initially a randomised controlled trial. Two hundred ten patients recruited from primary care psychiatric clinics with DSM‐III diagnosed dysthymic, generalised anxiety, and panic disorders were randomly allocated to either drug treatment (mainly antidepressants), cognitive‐behaviour therapy, or self‐help therapy over a 2 year period, irrespective of original diagnosis. Life events were recorded by using a standard procedure over the period 6 months before starting treatment and at five occasions over 2 years; 181 (86%) of the patients had follow‐up data and 76% maintained compliance with the original treatment allocated over the 2 years; and 155 of the 181 patients (86%) had at least one diagnostic change in this period. There was no difference in the number of diagnostic changes between the three original diagnostic groups, but dysthymic disorder changed more frequently to major depressive episode than did GAD or panic disorder (20;11;12) (%) and panic disorder changed more frequently to agoraphobia (with or without panic) than did dysthymia or GAD (18; 8; 6) (%). There was no relationship between loss events and depressive diagnoses or between addition events and anxiety diagnoses, but greater numbers of conflict events were associated with diagnostic change. More life events were associated with the flamboyant and dependent personality disorders, reinforcing other evidence that many life events are internally generated by personality characteristics and cannot be regarded as truly independent. Depression and Anxiety 11:105–113, 2000.

Clinical efficacy of paroxetine in resistant depression

The antidepressant effects of a specific reuptake inhibitor of 5-hydroxytryptamine (5-HT), paroxetine, were tested in 24 patients with resistant depression who had failed to respond to conventional antidepressants after at least 4 weeks of treatment. A novel exper imental design was chosen in which all patients had 12 weeks of treatment beginning and ending with placebo therapy with 6 weeks of active drug treatment at some point in between. Ratings of depressive symptoms were made using the Hamilton rating scale (HRS) for depression, and the checklist for unwanted effects and their severity was also recorded before and during treatment at 2 week intervals. The change from placebo to active paroxetine therapy was made using a double-blind procedure. Patients who made a significant placebo response in the first 2 weeks of treatment were excluded from further analysis; 20 patients completed the study and satisfied all criteria for inclusion. Both groups of showed a significant improvement in symptoms after 4 weeks of paroxetine therapy. There were no significant treatment differences between the groups, but improvement in symptoms occurred sig nificantly later in the patients who had a longer period of initial placebo therapy. The experimental design also allowed study of withdrawal effects after stopping active treatment. There was no increase in adverse effects, including a subgroup associated with withdrawal problems, either during treatment with paroxetine or after the drug was stopped. The results suggest that paroxetine is probably an effective antidepressant, is well tolerated and has few adverse effects.

Long-term outcome of hypochondriacal personality disorder

Hypochondriacal personality disorder diagnosed according to the Personality Assessment Schedule, a structured clinical interview, was related to outcome after 2 years and 5 years in a randomized, controlled trial of treatment of generalized anxiety, panic, and dysthymic disorders. Seventeen individuals (9%) from a population of 181 patients had hypochondriacal personality disorder and they experienced a significantly worse outcome than other patients, including those with other personality disorders, in terms of symptomatic change and health service utilization. This lack of improvement was associated with persistent somatization in hypochondriacal personality disorder. The results give further support to the belief that hypochondriacal personality disorder is a valid clinical diagnosis that has important clinical correlates, but further work is needed to establish the extent of its overlap with hypochondriasis as a mental state disorder.

Pharmacological treatment of personality disorders.

Therapists are only now just beginning to clear a way through the jungle of personality disorder and any recommendations about drug treatment have to be tentative and, to some extent, speculative. Nevertheless, it is reasonable to conclude that drug treatment, mainly in the form of antipsychotic agents, should be considered in borderline and antisocial personality disorders and also possibly in the schizotypal group. There is also growing evidence that two drugs used in the treatment of manic-depressive psychosis, lithium and carbamazepine, may have independent effects in controlling aggression and impulsiveness and be of value of borderline and antisocial personality disorders. In histrionic and dependent personality disorders, drug treatment is in general contraindicated and for the remaining group our ignorance of the possible benefit of the drugs is almost total. However, the negative effect of these personality disorders on response to treatment in the presence of depression, anxiety, and other abnormal mental state disorders suggests that drug treatment probably has little part to play in management of these particular personality disorders. A major deficiency in our knowledge, which can only be remedied by long-term studies that are extremely difficult to mount, is the recommended duration of treatment with drugs in personality disorder. No guidelines exist at present but now that some measure of efficacy has been established duration of treatment needs to be addressed.

Prescribing to drug misusers in practice—often effective, but rarely straightforward

Many reviews describe the effectiveness of methadone treatment in reducing illicit drug use and associated behaviours among opiate misusers. The strongest evidence includes social outcomes such as reduced debt and crime, and relates overwhelmingly to maintenance rather than detoxification treatment. Drug clinics are often dominated by individuals unable to withdraw fully from methadone, while the “harm reduction” model accepts some ongoing drug use, with attendant risks. Security measures are necessary to avoid abuse of treatments, but these may be undermined by the agenda of “partnerships with patients” in decision‐making. Buprenorphine appears both safer and less addictive than methadone, and lofexidine is effective as a non‐substitute detoxification method. Naltrexone can clearly reduce relapse rates, provided consumption is assured, while for individuals unable to detoxify or avoid euphoriant opiates, morphine and diamorphine are sometimes used. In non‐opiate misuse, clinical studies of a wide range of medications have produced relatively few positive findings.