Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. Hertfordshire Neuroscience Research Group.

Several case reports have engendered concern about the safety of coadministering lithium and selective serotonin reuptake inhibitor (SSRI) antidepressants and there are theoretical reasons to suppose that lithium and serotonergic antidepressants may be associated with dangerous interactions. Systematic reports regarding combination therapy with lithium and SSRI antidepressants were assimilated for the purpose of this review. Although there are many publications, few are directly informative as to safety and tolerability. A total of 503 patients are considered in systematic reports and, among these, no serious or life-threatening adverse events can be identified. Such data as there are demonstrate little potential for toxic interactions between lithium and SSRIs, although new, non-serious, adverse events do frequently arise. The evidence for the efficacy of addition of lithium to SSRIs in treatment refractory depression is only provisional.

A protocol for the pharmacologic treatment of major depression. A field test of a potential prototype.

BACKGROUND: Much attention is being given to developing clinical practice guidelines for management of mental health disorders. The aim of this study was to field test a prototype protocol for the pharmacologic treatment of Major Depression. METHOD: The protocol consisted of four, six week, treatment phases with critical choices in therapy defined by scores on the MADRS (Montgomery Asberg Depression Rating Scale). Observational data as collected on the behaviour of the protocol in terms of relevance, acceptability, ease of use and effectiveness. RESULTS: Effectiveness of the protocol was good for those patients who were retained within it, with three quarters of them attaining remission. However more than half of all patients dropped out-non attendance and adverse events being the most common reasons for this. CONCLUSION: The protocol for the treatment of Major Depression appeared relevant, easy to use and potentially effective. LIMITATION: Problems with non-adherence by both doctors and patients posed major challenges to the protocol's design. Such difficulties demonstrate the need to field test any proposed design as preconceptions about a protocol's performance may be misplaced. CLINICAL RELEVANCE: The protocol tested represents progress towards the goal of developing optimal strategies for the use of pharmacotherapeutic agents in the treatment of depression.

A preliminary study to examine the adequacy of long-term treatment of depression and the extent of recovery in general practice.

About 1% of patients in general practice take antidepressants for long periods. Many receive repeat prescriptions, without review. It might be assumed that these patients are well and are on adequate maintenance treatment. Our findings refute this assumption; of 78 patients on long-term repeats, only a third were in remission and a fifth had Beck Depression Inventory scores suggesting persisting syndromal major depression. Subtherapeutic dosing of classic tricyclics was the norm rather than the exception. Patients on long term antidepressant treatment need regular review and adequate treatment to ensure remission is maintained.

A review of the psychomotor effects of paroxetine.

All 10 placebo-controlled studies of the psychomotor effects of paroxetine are reviewed. The total number of subjects is 195. The majority of studies show little or no effect of paroxetine on psychomotor function. No adverse effects are apparent at the dose of 20 mg/day, although minor impairments can be identified at 40 mg/day. An overview of the data indicates that at the standard therapeutic dose of 20 mg/day, paroxetine has no psychomotor or behavioural toxicity.

Safety and tolerability of combined treatment with moclobemide and SSRIs: a systematic study of 50 patients.

Fifty major depressed patients, resistant to multiple pharmacotherapies, were treated by the addition of moclobemide (up to 600 mg/day) to paroxetine or fluoxetine (20 mg/day) for 6 weeks in an open study to assess tolerability. There were 188 adverse events: insomnia, dizziness, headache, nausea, dry mouth and myoclonic jerks were the most common. Many events were rated as severe. The high rate of adverse events suggest that there are clinically significant pharmacodynamic interactions between moclobemide and SSRIs. However the uncontrolled data on effectiveness is encouraging and the combination deserves further consideration as a strategy for treating intractable depression.

Safety and tolerability of combined treatment with moclobemide and SSRIs: a preliminary study of 19 patients.

Nineteen major depressed patients, resistant to previous pharmacotherapies, were treated by the addition of moclobemide (up to 600 mg/day) to paroxetine or fluoxetine (20 mg/day) for 6 weeks in an open study to assess the adverse events and tolerability. There were 77 emergent events, insomnia, headache, nausea and dizziness being the most common. Many events were rated as severe. The high rate of adverse events suggests that there may be clinically significant interactions between moclobemide and SSRIs. However, the uncontrolled data on effectiveness is encouraging and the combination deserves further attention as a strategy for treating intractable major depression.

Dimethylsulphoxide affects the organisation of microfilaments in the mouse oocyte.

The effect of dimethylsulphoxide (DMSO) on microfilament organisation has been studied in the mouse oocyte after staining with (NBD)-phallacidin. The cortical actin meshwork was disrupted by exposure of oocytes to 1.5 M DMSO at 37 degrees C, and this disruption was associated with changes in the cell surface, especially microvilli length and distribution, as observed by scanning electron microscopy. The irregular distribution of actin filaments observed also appears to lead to an irregular expansion of the cell after DMSO removal. However, when exposure to DMSO was combined with cooling, the effects on the microfilament system were much reduced. The reversibility of DMSO action is considered and the potential implications of microfilament disruption on the viability and functions of the oocyte discussed.