O. Lingjærde

Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations

Risperidone (RIS), a new neuroleptic with 5‐HT2‐ and dopamine D2 receptor‐blocking properties, was compared with perphenazine (PER) in a double‐blind, multicentre, parallel‐group study in 107 chronic schizophrenics with acute exacerbation. RIS 5‐15 mg or PER 16–48 mg daily was given for 8 weeks. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression. Seventy‐eight patients completed the trial; there was an equal number of dropouts on both drugs. The mean daily dose at endpoint was 8.5 mg RIS and 28 mg PER. The reduction in total PANSS score to endpoint did not differ significantly, although there was a tendency in favour of RIS. The number of patients with predominantly negative symptoms who showed at least 20% reduction in total PANSS score was significantly larger in the RIS group. Furthermore, the number of patients showing at least 20% reduction in Brief Psychiatric Rating Scale (BPRS) score (BPRS being a subscale of PANSS) was significantly larger in the RIS group. The hostility cluster of BPRS improved more on RIS than on PER in the endpoint analysis. The overall prevalence of side effects was fairly similar in the two groups.

Treatment of winter depression in Norway.: II. A comparison of the selective monoamine oxidase A inhibitor moclobemide and placebo

Thirty‐four patients with seasonal affective disorder, winter depression type (WD) were randomly distributed to receive the selective monoamine oxidase‐A inhibitor moclobemide (400 mg daily) or placebo in a double‐blind, parallel group study lasting for up to 14 weeks. Severity measures were the Montgomery‐Åsberg Depression Rating Scale (MADRS) extended with characteristic symptoms of WD; summed score of the “atypical” symptoms hypersomnia, hyperphagia and carbohydrate craving; and Clinical Global Impressions (CGI). After 3 weeks, patients with unsatisfactory response were switched to open moclobemide. Three patients on placebo dropped out before 3 weeks. Extended MADRS and CGI showed no significant difference between the groups at 3 weeks, whereas the atypical score was reduced significantly more on moclobemide than on placebo already after one week. Nonresponders after 3 weeks (9 of 16 on moclobemide and 7 of 15 on placebo) improved rapidly after being given open moclobemide. Predictor analysis showed a remarkably high negative correlation between improvement at 3 weeks (extended MADRS) and age in the placebo group and a strong, nonsignificant trend in the same direction in the moclobemide group. Dichotomizing the patients according to the median age (45 years) resulted in a somewhat better effect of moclobemide than placebo in the older age group. There were no significant differences in side effects between moclobemide and placebo.

Characteristics of winter depression in the Oslo area (60°N)

This is the first comprehensive description of winter depression (WD), as part of seasonal affective disorder (SAD), from Norway, and one of the very few from so far north. A total of 128 media‐recruited people had first been screened with the Seasonal Pattern Assessment Questionnaire and were thereafter personally interviewed. The criteria for DSM‐III‐R mood disorder, seasonal pattern, were satisfied by 85%, whereas 73% satisfied the criteria of Rosenthal et al. for SAD. Seven percent were diagnosed as subsyndromal SAD. The main characteristics of our patient group were in reasonable accordance with other clinical SAD materials: there were 81% women; the mean age was 44 years (range: 20 to 76); the mean age for SAD debut was 24 years (range: 4 to 71); and the duration of WD was most often from October to March or April. Only 12% had ever been manic or hypomanic in summer. During their WD, most patients suffered at least one of the symptoms hypersomnia, hyperphagia or carbohydrate craving; 16% also had a craving for fatty food in winter, but this may be considered “normal” at this northerly latitude.

Treatment of winter depression in Norway. I: Short- and long-term effects of 1500-lux white light for 6 days

Patients with seasonal affective disorder (winter depression) from the Oslo area (at about 60°N) recruited through mass media advertising were treated with 1500‐lx white full‐spectrum light for 2 h in the morning for 6 days. Their clinical state was assessed at baseline and 1, 3, 6, 10 and 14 weeks after commencement of treatment with an extended version of Montgomery‐Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression. Forty patients (35 women, 5 men, age range 24 to 64 years) completed 1 week of light treatment. A subgroup of 9 patients received light in addition to ongoing drug treatment. The mean reduction in total extended MADRS score at week 1 was 48% in patients receiving only light and 56% in patients receiving light in addition to drugs. In spite of the low dose of light given, this is comparable to other reported results using light treatment for winter depression. In contrast to most other studies, however, the improvement at week 1 was maintained for the rest of the season in most patients. Only 5 patients were given another light treatment course, and another 5 were switched to drug treatment due to their unsatisfactory response to light treatment.

Lactate-induced panic attacks: possible involvement of serotonin reuptake stimulation.

ABSTRACT– In panic disorder patients, panic attacks can be precipitated with great regularity by intravenous infusion of lactate. The mechanism behind this effect, as well as the mechanism behind the spontaneously occurring panic attacks, are unknown, however. The author draws attention to the fact that lactate as well as pyruvate stimulate serotonin uptake in human blood platelets, and suggests that lactate infusion may stimulate serotonin reuptake also in central serotonergic neurons, thereby decreasing serotonergic activity. This may possibly induce anxiety by reducing the inhibitory serotonergic influence on locus ceruleus. This mechanism ‐ which may not be the only one involved in lactate‐induced panic attacks ‐ would easily explain the effect of tricyclic antidepressants, like imipramine, against lactate‐induced panic.

Benzodiazepines in the treatment of schizophrenia: an updated survey

Reports on the effects of benzodiazepines in schizophrenia have appeared since the early 1960s. Conclusions drawn from these studies, most of which have been uncontrolled, have ranged from worse than placebo to better than neuroleptics. A critical appraisal of the literature seems to warrant the following main conclusions. Benzodiazepines alone, in conventional doses, have no convincing antipsychotic effect in schizophrenia, although they may reduce anxiety, tension and insomnia. However, very high doses of diazepam, and possibly other benzodiazepines, may have a symptomatic antipsychotic effect, especially in paranoid‐hallucinatory schizophrenics, also when given alone. Benzodiazepines, in conventional doses, can enhance the antipsychotic effect of neuroleptics in schizophrenics who have not responded satisfactorily to neuroleptics alone. This effect may be most conspicuous against hallucinations, but improvement may also be obtained from delusions, thought disturbances, some negative symptoms, anxiety and tension. Some benzodiazepines may be more effective than others in schizophrenia, but this has been insufficiently elucidated.

Dawn simulation vs. lightbox treatment in winter depression: a comparative study

Dawn simulation, with gradually increasing bedside light in the morning, has shown promising results as an alternative to bright light treatment for winter depression. To compare these treatments, 61 out‐patients with winter depression (20–70 years of age, 80% women) were randomized to receive either lightbox treatment with 1500–2500 lux white light for 2 h in the morning for 6 days on an out‐patient basis (n=34), or dawn simulation treatment in their homes, with 60 or 90 min of light augmentation time to 100–300 lux, for 2 weeks (n=27). Patients’ ratings of improvement on a visual analogue scale (correlating strongly with percentage reduction in an extended Montgomery‐Åsberg Depression Rating Scale (MADRS) score) at the end of treatment showed a mean of 40.0% (SD 27.7%) in the dawn simulation group and 57.4% (SD 29.9%) in the lightbox group (p=0.02). The majority of the patients in both groups maintained their improvement during a 9‐week follow‐up. Age, sex, current major depression or current use of antidepressants did not predict outcome in either group. No serious side‐effects were observed.

From clomipramine to mianserin: therapeutic relevance of interactions with serotonin uptake and storage, as studied in the blood platelet model

Inhibition of active serotonin uptake into neurones and platelets is a common effect of tricyclic and related antidepressants, and has been regarded as one of the more important mechanisms of action of such drugs. However, as is shown in this survey, the antidepressants vary widely in their potency as inhibitors of platelet serotonin uptake, and they also differ in the type of inhibition kinetics, from purely competitive to mixed competitive/non‐competitive. The therapeutic relevance of this effect is discussed. Serotonin uptake inhibition seems to be one of several mechanisms for obtaining the required normalization of monoamine dysfunction in depression. Analysis of efflux from platelets preloaded with a moderate amount of 14C‐serotonin provides information on the storage and compartmentation of serotonin in the platelets, and on the rate of efflux from the different compartments. When present during the preloading phase, some antidepressants seem to produce a relative increase in serotonin in the granular storage compartment when compared to the smaller cytoplasmic compartment. This effect is in some respects opposite to that exerted by reserpine, and possibly may be pharmacologically relevant.

SOME PHARMACOLOGICAL ASPECTS OF DEPOT NEUROLEPTICS

A depot neuroleptic may be defined as a neuroleptic which can be administered in such a form and in such a manner that one single dose gives a therapeutically effective tissue concentration for at least one week. There are two main ways of obtaining long-lasting tissue concentrations of a drug: ( 1 ) By the drug being taken up into the blood very slowly, and (2) By slow metabolism and/or elimination of the active drug. Often, a combination of these two mechanisms is utilized. Disregarding the mechanisms underlying the long-lasting effect, the depot preparations can conveniently be classified in the following way:

A double-blind comparison of moclobemide and doxepin in depressed general practice patients

A total of 56 patients attending a general practitioner for treatment of depression, most of whom met the criteria for major depression, were included in this double‐blind, parallel group, 6‐week study, in which the selective MAO‐A inhibitor moclobemide (MOC; maximum dose 600 mg) was compared with the tricyclic antidepressant doxepin (DOX; maximum dose 250 mg). Thirty patients on MOC and 23 on DOX were assessed after treatment for at least 1 week and are included in the response evaluation. Improvement was assessed primarily with the Montgomery‐Asberg Depression Rating Scale (MADRS). There were only 4 drop‐outs in the MOC group and three in the DOX group after 1 week. Overall improvement measures showed a nonsignificant difference in favor of DOX. Two factors were found to have prognostic significance: (1) previous or present panic attacks (10 patients in the MOC group and – by chance – only one in the DOX group) were associated with significantly lower improvement within the MOC group. Since we had no a priori hypothesis about this effect, it could be a chance finding. (2) Improvement was negatively correlated with age; this was statistically significant in the total group as well as in the MOC group, with a nonsignificant trend in the same direction in the DOX group. Side effects differed little between the two groups; only dryness of mouth appeared with markedly higher frequency in the DOX group.