Journal of Clinical Psychopharmacology最新文献

Background: In treatment-refractory schizophrenia, pre-dose plasma clozapine concentrations are, on average, lower in smokers than in nonsmokers. This may relate to the incidence of adverse drug reactions (ADR).

Methods: Generalized estimating equation analyses were used to investigate clozapine TDM data from 1993 to 2017 for ADR with ≥30 mentions on request forms.

Results: There were 1154 mentions of an ADR (1058 patients), 36,470 controls ("baseline" samples, 14,572 patients). In the ADR group, median plasma clozapine concentration (mg/L) was significantly lower in smokers (0.41, N=586) than nonsmokers (0.56, N=368) ( P <0.001). The constipation subgroup, for example, had higher median plasma clozapine concentrations [0.56 (0.22-1.27) mg/L] than the controls [0.45 (0.18-0.93) mg/L] ( P =0.025). Higher plasma clozapine concentrations were also associated with hypersalivation, hypotension, and neurological ADR (seizures and myoclonus), but no associations were found in relation to cardiac, low white cell count, metabolic, and nausea/vomiting subgroups. In the neurological ADR subgroup, plasma clozapine concentrations were higher in smokers ( P <0.001) and in nonsmokers ( P =0.019) compared with controls. In the constipation subgroup, plasma clozapine was only significantly higher in nonsmokers, while in the hypotension and sedation subgroups, the opposite applied. Plasma norclozapine showed a similar pattern of results to that of clozapine. The plasma clozapine:norclozapine ratio showed no consistent pattern between the ADR subgroups.

Implications: ADR such as constipation and seizures may be more likely to occur at lower plasma clozapine concentrations in smokers. The underlying mechanism(s) require further investigation.

Purpose/background: Previous studies among psychiatric patients have shown differences between men and women in psychotropic medication prescription patterns. The factors underlying these differences are still poorly understood. This exploratory study aimed to investigate a range of clinical and demographic factors in their contributions to explaining these gender differences.

Methods/procedures: In 2476 outpatients with a mental disorder (mean age 46.1 year, 58.2% women) enrolled in pharmacotherapy monitoring program, regression analyses were used to investigate the associations of gender with use of any psychotropic (yes/no), use of each separate psychotropic type (yes/no), number (0 to 4) and dosage of each used psychotropic. Next, clinical and demographic effect modifiers and explanatory/confounding factors of these associations were identified.

Findings/results: Frequencies of general psychotropic use, antidepressant use, anxiolytic use, as well as polypharmacy were significantly higher in women than in men across all ages (premenopausal, perimenopausal, and postmenopausal), with equal dosing of psychotropics, except for higher doses of mood stabilizers in men. Longer illness duration and having a partner were effect modifiers of the gender effect, while higher frequencies of an affective/anxiety diagnosis, higher somatic complaints and symptomatic distress, more previous mental health service (MHS) visits and no current occupation were explanatory factors.

Implications/conclusions: Psychotropic use and psychotropic polypharmacy were more common in women than in men. Women on psychotropic medications were more often diagnosed with affective/anxiety diagnoses, experienced more symptomatic distress and somatic complaints, and visited more healthcare services than men, reaffirming findings from previous studies. Future longitudinal studies should investigate in further detail whether these outcomes are cause or consequence of gender differences in psychotropic medication use.

Purpose/background: In patients with major depressive disorder (MDD), anxiety symptoms are common and associated with reduced treatment response. In an 8-week, phase 4, open-label study (ENGAGE), patients with MDD and inadequate antidepressant treatment response showed improvements in patient life engagement, depressive symptoms, and anxiety symptoms following treatment with adjunctive brexpiprazole 0.5 to 2 mg/d. This post hoc analysis of ENGAGE aimed to characterize the utility of adjunctive brexpiprazole in clinically relevant subgroups by baseline anxiety level.

Methods/procedures: Baseline anxiety subgroups were based on the 7-item Generalized Anxiety Disorder scale total score: no/mild (<10), moderate (10 to 14), and severe (>14). In each subgroup, changes in the 10-item Inventory of Symptomatology Self-Report (IDS-SR10) Life Engagement subscale score, IDS-SR total score, and other efficacy outcomes were determined. Safety was also analyzed.

Findings/results: One hundred twenty patients received adjunctive brexpiprazole, of whom 30 (25.0%) had no/mild anxiety, 43 (35.8%) had moderate anxiety, and 47 (39.2%) had severe anxiety at baseline. On IDS-SR10 Life Engagement subscale score and IDS-SR total score, improvements (nominal P<0.001) from baseline to week 8 were observed across all subgroups. Improvements were also observed on all other efficacy endpoints (nominal P<0.05 in all subgroups). Incidence of treatment-emergent adverse events was 76.7% (no/mild baseline anxiety), 72.1% (moderate baseline anxiety), and 57.4% (severe baseline anxiety). No new safety signals were observed.

Implications/conclusions: Over 8 weeks, adjunctive brexpiprazole was associated with improvements in patient life engagement and depressive symptoms, regardless of baseline anxiety level. This observation may assist clinical decision-making when treating patients with MDD with/without anxiety symptoms.