DESIGN AND METHODS: Four PPSs, including headache, chest pain, low back pain, and muscle pain, and subjective depressive symptoms were assessed using the Symptom Checklist-90-Revised.
FINDINGS: Out of 528 participants, 390 (73.9%) had at least one PPS. After adjusting for sex, depression severity, disability, fatigue, physical health status, and mental health status, PPSs were found to be associated with crying easily, blaming oneself, feeling lonely, feeling blue, and worrying too much.
PRACTICAL IMPLICATIONS: Almost three-quarters of Asian patients with MDD experience PPSs. PPSs are associated with some subjective feelings of depression.
METHODS: Patients received paliperidone palmitate 1-monthly (PP1M, 100/150 mg eq.) or paliperidone palmitate 3-monthly (PP3M, 350/525 mg eq.) during the maintenance phase and entered a 12-month double-blind (DB) phase, wherein they were randomized (2:1) to PP6M (700/1000 mg. eq.) or PP3M (350/525 mg eq.). Subgroup analysis was performed for 90 (12.7%) patients from Asia region (India, Taiwan, Malaysia, Hong Kong, and Korea). Primary endpoint was time-to-relapse during DB phase (Kaplan-Meier estimates). Secondary endpoints were changes from baseline in Positive and Negative Syndrome Scale, Clinical Global Impression-Severity scale, Personal and Social Performance (PSP) scale score.
RESULTS: In Asian subgroup, 91.9% (82/90) of patients completed DB phase (PP6M: 54/62 [87%]; PP3M: 28/28 [100%]). Median time-to-relapse was "not-estimable" due to low relapse rates in both groups. Estimated difference (95% confidence interval [CI]) between relapse-free patients in PP6M and PP3M groups of Asian subgroup was -0.1% [-8.5%, 8.4%] (global study population: -2.9% [-6.8%, 1.1%]). Mean change from baseline in secondary efficacy parameters was comparable between both groups, similar to the global study population. The incidence of extrapyramidal symptoms was higher in the Asian subgroup than in the global study population.
CONCLUSION: Consistent with the global study population, PP6M was noninferior to PP3M in preventing relapse in patients with schizophrenia from the Asia region. Findings suggest the possibility of switching from PP1M/PP3M to twice-yearly PP6M without loss of efficacy and with no unexpected safety concerns.
METHODS: Following a thematic literature review and pre-meeting survey, a SEA expert panel comprising 13 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA Appropriateness Method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management.
RESULTS: The expert panel agreed that "pharmacotherapy-resistant depression" (PRD) is a more suitable term for TRD and defined it as "failure of two drug treatments of adequate doses, for 4-8 weeks duration with adequate adherence, during a major depressive episode". A stepwise treatment approach should be employed for the management of PRD - treatment strategies can include maximizing dose, switching to a different class, and augmenting or combining treatments. Non-pharmacological treatments, such as electroconvulsive therapy and repetitive transcranial magnetic stimulation, are also appropriate options for patients with PRD.
CONCLUSION: These consensus recommendations on the operational definition of PRD and treatment principles for its management can be adapted to local contexts in the SEA countries but should not replace clinical judgement. Individual circumstances and benefit-risk balance should be carefully considered while determining the most appropriate treatment option for patients with PRD.
METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase.
RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]).
CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.
AIM: To assess plasma testosterone and sexual function in Southeast Asian men on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT).
METHODS: 76 sexually active men on MMT (mean age = 43.30 ± 10.32 years) and 31 men on BMT (mean age = 41.87 ± 9.76 years) from a Southeast Asian community were evaluated using plasma total testosterone (TT) and prolactin levels, body mass index, social demographics, substance use measures, and depression severity scale.
OUTCOMES: Prevalence and associated factors of TT level lower than the reference range in men on MMT or BMT.
RESULTS: More than 1 third of men (40.8%, n = 31) on MMT had TT levels lower than the reference range, whereas 1 fourth of men (22.6%, n = 7) on BMT did. At univariate analysis, MMT vs BMT (β = 0.298, adjusted R2 = 0.08, P = .02) and body mass index (β = -0.23, adjusted R2 = 0.12, P = .02) were associated with changes in TT after stepwise regression. There were no significant associations with age; Opiate Treatment Index Q scores for alcohol, heroin, stimulant, tobacco, or cannabis use and social functioning domain; education levels; hepatitis C status; and severity of depression. Prolactin level did not differ between the MMT and BMT groups.
CLINICAL IMPLICATIONS: The sex hormonal assay should be used regularly to check men on MMT.
STRENGTHS AND LIMITATIONS: This is the first study conducted in the Southeast Asian community. Our study was limited by the lack of a healthy group as the reference for serum levels of testosterone and prolactin.
CONCLUSIONS: The findings showed that plasma testosterone levels are lower in MMT than in BMT users. Hence, men who are receiving MMT should be screened for hypogonadism routinely in the clinical setting. Yee A, Loh HS, Danaee M, et al. Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment. J Sex Med 2018;15:159-166.