Björn Mårtensson

CSF monoamine metabolites in melancholia

ABSTRACT– The neurotransmitter metabolites 5‐hydroxyindoleacetic acid (5‐HIAA), homovanillic acid (HVA) and 4‐hydroxy‐3‐methoxy‐phenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured by mass fragmentography in 83 patients with melancholia (diagnosed by the Newcastle Inventory and the Research Diagnostic Criteria), and 66 healthy volunteer controls. After adjustment by analysis of covariance for differences between the subject groups in body height, age and sex distribution, significantly (P < 0.001) lower concentrations of 5‐HIAA and HVA were found in the melancholia patients than in the controls. HMPG did not differ between the groups. The differences could not be accounted for by differences in timing or examination techniques, and not by previously administered drugs (all patients were drug‐free at the examination, but a minority had taken small amounts of psychotropic drugs prior to the wash‐out period). The differences persisted after excluding the suicidal patients. There were no clear‐cut differences between unipolar and bipolar patients. It is suggested that the reduced concentrations of 5‐HIAA and HVA in the melancholic patients may be due to altered serotonin and/or dopamine functions in the central nervous system, which may be connected with an increased vulnerability to certain types of affective illness.

Lower 3H-imipramine binding in platelets from untreated depressed patients compared to healthy controls

3H-Imipramine binding in platelets was measured in 63 severely depressed hospitalized patients, who had been drug free (with the exception of moderate doses of benzodiazepines) for at least 1 month, and in 53 healthy control subjects of comparable age and sex distribution. Bmax of 3H-imipramine binding was significantly lower in the depressed subjects (1012 +/- SD 295 vs. 1123 +/- SD 178 fmole/mg protein). Depressed patients who had attempted suicide by violent means tended to have higher Bmax than nonviolent attempters.

Effects of fluoxetine treatment of platelet 3H-imipramine binding, 5-HT uptake and 5-HT content in major depressive disorder

Platelet 3H-imipramine binding, serotonin (5-HT) uptake and 5-HT concentrations were studied in 14 hospitalized patients with depressive disorder following 6 weeks of treatment with a selective 5-HT uptake blocker, fluoxetine. After 3 weeks of treatment there was a significant decrease in Bmax of 3H-imipramine binding and a significant increase in Kd. A highly significant decrease in Vmax of 5-HT uptake was seen after 3 weeks of treatment which was accompanied by a slight increase in Km. At the same time the platelet 5-HT content was significantly reduced by about 90% of its original level. The platelet 5-HT content continued to decrease with further treatment while there was a tendency for Vmax to return to pretreatment levels. The affinity of the 5-HT uptake carrier continued to decrease significantly. There was no further significant change in Bmax of 3H-imipramine binding during further treatment, although there was an increase in Bmax in the majority of patients. The changes in Bmax and Vmax were closely associated throughout the treatment. In some cases the changes in different platelet parameters correlated with the changes in depression rating scores during treatment, but this correlation did not reach statistical significance.

A comparison of propofol and methohexital as anesthetic agents for ECT: Effects on seizure duration, therapeutic outcome, and memory

The effects of the anesthetic agents propofol and methohexital on seizure duration, clinical outcome, recovery, and memory in electroconvulsive therapy (ECT) were studied in a double-blind trial. The study comprised 53 patients, 47 patients with major depression and six patients with other diagnoses according to DSM-III. Several recent clinical studies with a crossover design have shown a reduced seizure duration for anesthesia with propofol in comparison with both methohexital and thiopental. Propofol significantly reduced the seizure duration in this study without reducing the therapeutic outcome as measured by the Montgomery-Asberg Depression Rating Scale. Propofol did not significantly alter the length of the course of ECT; however, a slightly prolonged course for women cannot be completely ruled out. There were no significant differences between the two agents in effects on recovery times after anesthesia and on anterograde memory. In general, it seems that propofol is as effective as methohexital as an induction agent for ECT.

Effects of clomipramine treatment on cerebrospinal fluid monoamine metabolites and platelet 3 H‐imipramine binding and serotonin uptake and concentration in major depressive disorder

In an open study of 12 inpatients who met the DSM‐III criteria for a major depressive episode, the effects of clomipramine (CI) on the monoamine metabolites 5‐hydroxyindoleacetic acid (5‐HIAA), homovanillic acid (HVA), 4‐hydroxy‐3‐methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured simultaneously with the effects on 3H‐imipramine binding, serotonin (5‐HT) uptake and 5‐HT concentration in platelets after 3 and 6 weeks of treatment. Drug (CI and desmethylclomipramine) plasma concentrations were determined. The concentrations of 5‐HIAA and HMPG decreased substantially, and the concentration of HVA remained unchanged. There was also a large and significant reduction of the number of imipramine binding sites (Bmax and of the platelet 5‐HT concentration. The 5‐HT uptake was not measurable after 3 weeks of treatment. None of the parameters changed significantly between weeks 3 and 6. There were no significant correlations between antidepressant effect (measured by the Montgomery‐Åsberg Depression Rating Scale) and plasma drug concentrations, although a tendency to a significant correlation between antidepressant effect and CI was observed at 3 weeks. There were no significant intercorrelations between the different 5‐HT parameters and no other significant correlations between the biochemical measures and clinical outcome.

Bright white light therapy in depression: A critical review of the evidence

BACKGROUND Light therapy is an accepted treatment option, at least for seasonal affective disorder (SAD). Our aim was to critically evaluate treatment effects of bright white light (BWL) on the depressive symptoms in both SAD and non-seasonal depression. METHODS The systematic review was performed according to the PRISMA guidelines. PubMed, Embase, and PsycINFO were searched (December 1974 through June 2014) for randomized controlled trials published in peer-reviewed journals. Study quality was assessed with a checklist developed by the Swedish Council on Technology Assessment in Health Care. Only studies with high or medium quality were used in the meta-analyses. RESULTS Eight studies of SAD and two studies of non-seasonal depression met inclusion and quality criteria. Effects on SAD were estimated in two meta-analyses. In the first, week by week, BWL reached statistical significance only at two and three weeks of treatment (Standardized Mean Difference, SMD: -0.50 (-CI 0.94, -0.05); -0.31 (-0.59, -0.03) respectively). The second meta-analysis, of endpoint data only, showed a SMD of -0.54 (CI: -0.95, -0.13), which indicates an advantage for BWL. No meta-analysis was performed for non-seasonal depression due to heterogeneity between studies. LIMITATIONS This analysis is restricted to short-term effects of BWL measured as mean changes in scores derived from SIGH-SAD, SIGH-SAD self-report, or HDRS rating scales. CONCLUSIONS Most studies of BWL have considerable methodological problems, and the results of published meta-analyses are highly dependent on the study selection. Even though quality criteria are introduced in the selection procedures of studies, when the results are carefully scrutinized, the evidence is not unequivocal.

Memory effects of clomipramine treatment: Relationship to CSF monoamine metabolites and drug concentrations in plasma

Performance on tasks tapping automatic and voluntary aspects of memory, attention, and motor speed was examined in 14 patients with major depressive disorder, before and after 3 weeks of treatment with clomipramine (150 mg/day), a potent serotonin and noradrenaline uptake blocker with anticholinergic side effects. Performance on tasks requiring frontal functions improved or did not change, whereas verbal learning and retention, where hippocampal functioning is critical, were impaired. The latter tasks were negatively related to cerebrospinal fluid (CSF) 5-HIAA levels and plasma concentration of clomipramine. The results provide further support for the regulatory role of monoaminergic systems in cognition. Furthermore, we found the automatic-voluntary capacity distinction less heuristically useful. Physiological mechanisms regulating different aspects of cognition and memory appeared to be more closely related to the type of task used than to its capacity-demanding properties.

Undetected depression in primary healthcare: occurrence, severity and co-morbidity in a two-stage procedure of opportunistic screening.

Background: Depression often remains undetected in primary healthcare, and a two-stage screening procedure has been recommended for future research on the recognition, management and outcome of these patients. The aim of this study was to analyse the occurrence and the severity of depression, as well as gender, age and psychiatric co-morbidity in patients with previously undetected depression using a screening questionnaire followed by a diagnostic interview for detecting depression among patients visiting primary healthcare. Methods: All patients visiting a primary healthcare centre during a period of 10 days were asked to fill in the self-rating version of the Montgomery–Åsberg Depression Rating Scale. Patients with a score of 12 or more were invited to participate in a structured diagnostic interview based on the Primary Care Evaluation of Mental Disorders. Results: Out of 221 (=N) participants, 45 (20.4%) patients showed signs of depression (scores of 12 or more). Of these 45 patients, 31 consented to the structured interview, and of those, 28 (12.7%) fulfilled the criteria for depression, 17 (7.7%) had a major depression and 11 (5.0%) had a mixed depression–anxiety condition. Conclusions: The rate of undetected depression in primary healthcare was considerable. The majority of these patients had a major depression. Psychiatric co-morbidity among depressed patients was almost universal. The two-stage procedure of opportunistic screening with the Montgomery–Åsberg Depression Rating Scale and the Primary Care Evaluation of Mental Disorders seems to be a feasible method for detecting these patients in primary healthcare.

The use of selective serotonin reuptake inhibitors among Swedish psychiatrists: Results Of A Questionnaire

A questionnaire concerning the use of selective serotonin reuptake inhibitors (SSRIs), in part as a follow-up to a previous inquiry, was distributed to the members of the Swedish Psychiatric Association. The inquiry was distributed in June 1995 and consisted of 21 questions. Of the 1357 distributed questionnaires, 648 were returned (48%). SSRIs are reported to be, without any comparison, the commonest alternative in treatment of major depression, which is in contrast to the result of the previous questionnaire distibuted in 1993, when tricyclic antidepressants (TCAs) still were the main alternative. Most of the replying psychiatrists (65%) considered the antidepressant effect of the SSRIs, in general, to be comparable with that of the TCAs, but only 20% considered SSRIs to be comparable in treatment of severe depressions (melancholia). The use of SSRIs for several other indications besides major depression seems to be rather common, even though SSRIs are not approved for most of these indications. The mos...

Effects of Hesel-coil deep transcranial magnetic stimulation for depression - a systematic review.

Abstract Background: One third of the depressed patients are not improved by antidepressant drugs and psychological treatments, and there is a need for additional treatments. Repetitive transcranial magnetic stimulation (rTMS) is being developed towards an alternative in treatment-resistant depression. Deep transcranial stimulation (dTMS) with the Hesel-coil (H-coil) is a further development of rTMS aiming to enhance the effect by getting the magnetic pulses to penetrate deeper into the brain. Aims: This report aims to assess the evidence-base for dTMS for depression. The report also includes an assessment of the ethical and economic aspects involved. Methods: A systematic review of the effects of H-coil dTMS on depression was conducted and the scientific support was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Results: Only one controlled study was identified. In the sham-controlled randomized study, 212 participants with major depression that had not responded to antidepressant medication were enrolled. A two-point superiority in Hamilton Depression Rating Scale was observed in the dTMS arm vs the sham-arm at 4 weeks, but the difference was not statistically significant. No serious adverse events were reported apart from rare cases of epileptic seizures. Conclusions: The existing scientific support for H-coil dTMS therapy for depression is insufficient. The clinical implication is that the use of dTMS in depression should be restricted to the framework of clinical trials pending further studies. Fortunately, additional studies are underway and the evidence base should presumably improve over the next several years.