A workshop was convened by a panel of psychiatrists, diabetologists and pharmacists from major Belgian hospitals to review the latest information relating to the risks with second-generation antipsychotics (SGA) for the development of metabolic disorders, especially impaired glucose tolerance, diabetes mellitus and dyslipidemia. The panelists sought to formulate recommendations for practising psychiatrists when initiating and maintaining therapy with SGA, and for the switch of SGA or initiation of further treatment if metabolic complications occur. In addition, recommendations for counselling of the patient and for the cooperation between the psychiatrist and the general physician or diabetologist, respectively, were provided.

OBJECTIVE The Seroquel Patient Evaluation on Changing Treatment Relative to Usual Medication (SPECTRUM) study assessed the efficacy and tolerability of quetiapine (Seroquel™) in patients with schizophrenia switched from treatments providing suboptimal outcomes. METHODS This was an international, open-label, non-comparative study, designed with titration to 400 mg/day quetiapine over 7 days, then flexible dosing (300-750 mg/day) for 11 weeks. Efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS); Clinical Global Impression (CGI) Severity of Illness and Global Improvement scores; and the Calgary Depression Scale for Schizophrenia (CDSS). Clinical benefit and tolerability were also assessed. RESULTS The mean modal dose of quetiapine was 505 mg/day; 509 patients switched to quetiapine from olanzapine (13%), risperidone (11%), conventional antipsychotics (37%) and combinations of antipsychotics (28%), amongst others. Significant decreases in CGI Severity of Illness and PANSS scores and a significant improvement in CDSS score resulted from the switch (all P<0.001 versus baseline). There were significant reductions in extrapyramidal symptoms (EPS) on the Simpson-Angus Scale (SAS) and Barnes Akathisia Scale (BAS) (both P<0.001 versus baseline) and a low incidence of EPS-related adverse events (4.7%). CONCLUSION Results indicate that switching to quetiapine was clinically beneficial for patients with poor efficacy or intolerable side effects on their previous antipsychotic medication.

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The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P = 0.01) including five individual items, Hamilton depression scale (P = 0.002) including ten individual items, CGI of severity (P = 0.01) and therapeutical index (P = 0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P = 0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P = 0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.

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A multicenter study compared the antidepressant efficacy and the tolerance of two doses of milnacipran (50 mg and 100 mg/day) and amitriptyline (150 mg/day) in three parallel groups of 45 major depressive inpatients defined by Research Diagnostic Criteria. After a wash-out period of 4-7 days on placebo with lorazepam and/or nitrazepam if necessary, patients were randomly assigned to a daily dose of milnacipran 50 mg, milnacipran 100 mg or amitriptyline 150 mg reached on the 5th day and then stable over a 4-week period, with weekly assessments by means of the Montgomery and Asberg depression scale, the Hamilton depression scale, the Clinical Global Impressions (CGI) and the Target Emergent Signs and Symptoms. Results showed significant superiority of both milnacipran 100 mg/day and amitriptyline over milnacipran 50 mg/day at the end of the treatment period. However, amitriptyline induced a nonsignificant trend toward more rapid improvement after 2 weeks of treatment, mainly based on items related to insomnia, supporting more sedative properties of amitriptyline as compared to milnacipran. Anticholinergic side-effects were significantly lower with milnacipran than with amitriptyline, explaining why milnacipran 100 mg exhibited at the end of the treatment period, a nonsignificantly better efficacy index on the CGI. Moreover, in contrast to milnacipran, amitriptyline was responsible for a significant decrease in blood pressure and a significant weight gain.

A multicentre study compared the antidepressant efficacy and the tolerance of milnacipran (200 mg/d) and amitriptyline (1 50 mg/d) in two parallel groups of 43 major depressive inpatients, endogenous subtype, as defined by Research Diagnostic Criteria. The duration of the study was 4 weeks, with weekly assessments by means of the Montgomery and Asberg depression scale (MADS), the Hamilton depression scale, the Clinical Global Impressions (CGI) and a checklist of symptoms and side-effects. Results showed similar improvement in both groups but better tolerance with milnacipran (less drowsiness and anticholinergic side-effects), reflected in the better scores on the therapeutic index of the CGI. The clinical profile of the two drugs was somewhat different with more transitory sedation with amitriptyline and more improvement in concentration difficulties with milnacipran during the first weeks of the study associated with more effect on retardation with milnacipran at the end of the study.

A post hoc analysis of the SPECTRUM trial was carried out to evaluate whether the improvements in efficacy and tolerability gained on switching to quetiapine occurred consistently for patients previously treated with either: haloperidol (n = 43); olanzapine (n = 66); or risperidone (n = 55) monotherapy. Patients were initiated with quetiapine to 400 mg/day over 7 days, and then flexibly dosed (300-750 mg/day) for 11 weeks. The mean (SD) modal dose of quetiapine was 501 (138) mg/day in the haloperidol subgroup, 472 (147) mg/day in the olanzapine subgroup and 485 (141) mg/day in the risperidone subgroup at the study endpoint. Switching to quetiapine induced significant improvements from baseline in PANSS scores, with least square mean changes in total scores of -32.5, -15.4, and -18.5 for patients previously treated with haloperidol, olanzapine and risperidone, respectively, (all p < 0.001 vs baseline). Significant improvements were also noted in CDSS scores, particularly for patients clinically depressed at baseline (all p < 0.001 vs baseline). There were significant reductions in EPS on the SAS and BAS for all subgroups (all p < 0.001 vs baseline). Switching to quetiapine produced efficacy and tolerability benefits regardless of whether their previous antipsychotic was haloperidol, olanzapine or risperidone.