Theta burst stimulation for depression: a systematic review and network and pairwise meta-analysis.

In clinical practice, theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial magnetic stimulation (rTMS), as it allows for the delivery of more stimuli in less time and at similar intensities. To date, accelerated treatment plans according to various continuous (cTBS) and intermittent TBS (iTBS) protocols for depression have been proposed. To investigate which of the TBS protocols provided a favorable risk-benefit balance for individuals with depression, this systematic review and random-effects model network meta-analysis was conducted. The study outcomes included response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, incidence of switch to mania, and incidence of headache/discomfort at treatment site. In this meta-analysis, a total of 23 randomized controlled trials (n = 960, mean age = 41.88 years, with 60.78% females) were included. Approximately 69.57% of the trials included individuals with an exclusive diagnosis of major depressive disorder. The following six TBS protocols (target) were evaluated: cTBS (right-dorsolateral prefrontal cortex [R-DLPFC]), cTBS (R-DLPFC) + iTBS (left-DLPFC [L-DLPFC]), iTBS (L-DLPFC), iTBS (L-DLPFC) + iTBS (R-DLPFC), iTBS (left-dorsomedial prefrontal cortex) + iTBS (right-dorsomedial prefrontal cortex), and iTBS (occipital lobe). Compared to sham, cTBS (R-DLPFC) + iTBS (L-DLPFC), iTBS (L-DLPFC), and iTBS (occipital lobe) had a higher response rate (k = 23); cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) dominated in the depression symptom improvement (k = 23); and iTBS (L-DLPFC) had a higher remission rate (k = 15). No significant differences were found for all-cause discontinuation rate (k = 17), incidence of switch to mania (k = 7), and incidence of headache/discomfort at treatment site (k = 10) between any TBS protocols and sham. Thus, cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) demonstrate favorable risk-benefit balance for the treatment of depression.

Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis.

A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.

Discontinuation Rate of Lurasidone and Quetiapine Extended Release in Bipolar Depression.

INTRODUCTION: Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317). METHODS: This is a retrospective cohort study. RESULTS: Although the time to all-cause discontinuation was estimated using the Kaplan-Meier survival curve with log-rank tests to compare treatment groups, no difference was found (p=0.317). The Cox proportional hazard model revealed that only the presence of adverse events (AEs) is associated with increased treatment discontinuation (p<0.0001). The most common AEs were akathisia for LUR (17.7%) and somnolence for QUE-ER (34.7%). In other Cox models divided by LUR or QUE-ER, the presence of akathisia or somnolence was associated with increased LUR (p=0.0205) or QUE-ER (p<0.0001) discontinuation, respectively. DISCUSSION: The acceptability of both antipsychotics to bipolar depression in clinical practice may be similar. However, specific AEs for each antipsychotic (LUR: akathisia and QUE-ER: somnolence) were associated with high treatment discontinuation.

Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials.

A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.

Mood stabilizers and/or antipsychotics for bipolar disorder in the maintenance phase: a systematic review and network meta-analysis of randomized controlled trials.

We searched Embase, PubMed, and CENTRAL from inception until 22 May 2020 to investigate which antipsychotics and/or mood stabilizers are better for patients with bipolar disorder in the maintenance phase. We performed two categorical network meta-analyses. The first included monotherapy studies and studies in which the two drugs used were specified (i.e., aripiprazole, aripiprazole once monthly, aripiprazole+lamotrigine, aripiprazole+valproate, asenapine, carbamazepine, lamotrigine, lamotrigine+valproate, lithium, lithium+oxcarbazepine, lithium+valproate, olanzapine, paliperidone, quetiapine, risperidone long-acting injection, valproate, and placebo). The second included studies on second-generation antipsychotic combination therapies (SGAs) (i.e., aripiprazole, lurasidone, olanzapine, quetiapine, and ziprasidone) with lithium or valproate (LIT/VAL) compared with placebo with LIT/VAL. Outcomes were recurrence/relapse rate of any mood episode (RR-any, primary), depressive episode (RR-dep) and manic/hypomanic/mixed episode (RR-mania), discontinuation, mortality, and individual adverse events. Risk ratios and 95% credible interval were calculated. Forty-one randomized controlled trials were identified (n = 9821; mean study duration, 70.5 ± 36.6 weeks; percent female, 54.1%; mean age, 40.7 years). All active treatments other than carbamazepine, lamotrigine+valproate (no data) and paliperidone outperformed the placebo for RR-any. Aripiprazole+valproate, lamotrigine, lamotrigine+valproate, lithium, olanzapine, and quetiapine outperformed placebo for RR-dep. All active treatments, other than aripiprazole+valproate, carbamazepine, lamotrigine, and lamotrigine+valproate, outperformed placebo for RR-mania. Asenapine, lithium, olanzapine, quetiapine, and valproate outperformed placebo for all-cause discontinuation. All SGAs+LIT/VALs other than olanzapine+LIT/VAL outperformed placebo+LIT/VAL for RR-any. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-dep. Aripiprazole+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for RR-mania. Lurasidone+LIT/VAL and quetiapine+LIT/VAL outperformed placebo+LIT/VAL for all-cause discontinuation. Treatment efficacy, tolerability, and safety profiles differed among treatments.

Comparative Efficacy and Acceptability of 3 Repetitive Transcranial Magnetic Stimulation Devices for Depression: A Meta-Analysis of Randomized, Sham-Controlled Trials.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been employed worldwide for therapy-resistant depression. The Food and Drug Administration has approved a number of therapeutic devices for treating major depressive disorder; however, no studies have examined the differences in efficacy and acceptability among commercially available stimulation devices. The aim of our study was to compare the efficacy and acceptability of 3 stimulation devices (NeuroStar, MagPro, and Magstim) for depressive disorders. METHODS: Our study included 31 randomized sham-controlled trials of high-frequency rTMS included in the network meta-analysis by Brunoni. We calculated the risk ratio and 95% confidence intervals, comparing each device with sham for the endpoints of response rate, remission rate, and all-cause discontinuation. We then analyzed the differences among the devices in effect size for those endpoints. RESULTS: After determining the effect sizes for the endpoints, we found no statistically significant subgroup differences in the response rates, all-cause discontinuation, or remission rates among the devices (p = 0.12, p = 0.84, and p = 0.07, respectively). CONCLUSION: Our results suggest similar efficacy and acceptability for the 3 stimulation devices. Future studies need to perform head-to-head comparisons of the efficacy and acceptability of the stimulation devices for treating depression using the same stimulation protocols.

Aripiprazole Once-Monthly Versus Oral Aripiprazole for Schizophrenia in the Maintenance Phase: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: To examine whether aripiprazole once-monthly (AOM) was more beneficial than oral aripiprazole (OARI) in the treatment of adults with schizophrenia during the maintenance phase. METHODS: We performed a systematic review and network meta-analysis of double-blind, randomized controlled trials that included two of the following treatments: AOM, OARI, and placebo. RESULTS: We identified four studies involving 1830 adults. Relapse rates at 26 weeks were lower for both AOM (odds ratio [OR] 0.240, 95% confidence interval [CI] 0.169-0.341) and OARI (OR=0.306, 95%CI=0.217-0.431) than for placebo, although their treatment outcomes did not differ significantly (OR=0.786, 95%CI=0.529-1.168). Rates of all-cause discontinuation were also lower with AOM (OR=0.300, 95% CI=0.227-0.396) and OARI (OR=0.441, 95%CI=0.333-0.582) than with placebo. The rate of all-cause discontinuation was lower with AOM than with OARI (OR=0.681, 95% CI=0.529-0.877)]. Other outcomes did not differ significantly between AOM and OARI. DISCUSSION: Although both AOM and OARI were efficacious in the treatment of schizophrenia during the maintenance phase, AOM was better accepted than OARI.

Discontinuation and remission rates and social functioning in patients with schizophrenia receiving second-generation antipsychotics: 52-week evaluation of JUMPs, a randomized, open-label study.

AIM: Globally, evidence from short-term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long-term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large-scale, long-term naturalistic study to present pivotal 52-week data on the continuity of second-generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone). METHODS: JUMPs was an open-label, three-arm, randomized, parallel-group, 52-week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality-of-life scores [Personal and Social Performance Scale (PSP) and EuroQol-5 dimensions], and safety. RESULTS: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin. CONCLUSION: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan.

Recurrence rates in stable bipolar disorder patients after drug discontinuation v. drug maintenance: a systematic review and meta-analysis.

BACKGROUND: This random-effects model meta-analysis of double-blind, randomized placebo-controlled trials compared recurrence rates in bipolar disorder (BD) patients between antipsychotic/mood stabilizer discontinuation and maintenance groups. METHODS: We conducted systematic literature search of Embase, PubMed, and CENTRAL databases without language restriction from inception until 22 May 2020. Independent investigators assessed studies and extracted data. We calculated risk ratios (RRs) and numbers needed to benefit or harm (NNTB/NNTH). Primary outcome was the recurrence rate of any mood episode at 6 months. Secondary outcomes were recurrence rates of depressive episodes and manic/hypomanic/mixed episodes and all-cause discontinuation at 6 months. We also investigated these outcomes at 1, 3, 9, 12, 18, and 24 months. RESULTS: We identified 22 studies (n = 5462) receiving aripiprazole, asenapine, divalproex, long-acting injectable (LAI)-aripiprazole, LAI-risperidone, lamotrigine, lithium, olanzapine, paliperidone, or quetiapine. Mean study duration was 64.50 ± 69.35 weeks. The maintenance group demonstrated lower recurrence rates of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes as well as reduced all-cause discontinuation at every observational point. The RRs (95% confidence interval, NNTB/NNTH) of recurrence rate at 6 months were 0.61 (0.54-0.70, 5) for any mood episode, 0.72 (0.60-0.87, 13) for depressive episodes, and 0.45 (0.36-0.57, 6) for manic/hypomanic/mixed episodes. The RR for all-cause discontinuation at 6 months was 0.71 (0.61-0.82, 6). CONCLUSIONS: Maintaining drug treatment during clinically stable BD prevented recurrence for up to 24 months. Discontinuation of medications for ⩾1 month significantly increased recurrence risk. However, 47.3% of patients who discontinued drugs for 6 months did not experience recurrence.

Effects of a conventional mood stabilizer alone or in combination with second-generation antipsychotics on recurrence rate and discontinuation rate in bipolar I disorder in the maintenance phase: A systematic review and meta-analysis of randomized, placebo-controlled trials.

OBJECTIVES: A systematic review and meta-analysis of double-blind, randomized placebo-controlled trials were conducted to examine how soon an increase in recurrence risk could be observed among bipolar I disorder (BDI) patients who were clinically stable with the combination therapy of mood stabilizers with second-generation antipsychotics (SGA+MS) treatment following second-generation antipsychotics discontinuation (i.e., MS alone) compared with SGA+MS maintenance. METHODS: Embase, PubMed, and CENTRAL databases were used for systematic literature searches until May/22/2020. The primary outcome was the recurrence rate of any mood episode at 6 months. The secondary outcomes were the recurrence rates of manic/hypomanic/mixed and depressive episodes and all-cause discontinuation at 6 months. The recurrence rates at 1, 2, 3, 9, and 12 months were also investigated. RESULTS: Eight studies (mean study duration = 58.25 ± 33.63 weeks) were identified (SGA+MS group [n = 1,456: 3 aripiprazole+MS studies, 1 lurasidone+MS study, 1 olanzapine+MS study, 2 quetiapine+MS studies, 1 ziprasidone+MS study] and placebo+MS group [n = 1,476]). Pooled SGA+MS exhibited lower recurrence rates of any mood episode, manic/hypomanic/mixed episodes, and depressive episodes as well as reduced all-cause discontinuation at every observational point. The risk ratios (95% confidence interval) of the recurrence rate at 6 months were 0.51 (0.39-0.86) for any mood episode, 0.42 (0.30-0.59) for manic/hypomanic/mixed episodes, and 0.39 (0.28-0.54) for depressive episodes. The RR for all-cause discontinuation was 0.67 (0.50-0.89). Both aripiprazole+MS and quetiapine+MS outperformed placebo+MS in the recurrence of any mood, manic/hypomanic/mixed, and depressive episodes at 6 months. CONCLUSIONS: SGA+MS prevented recurrence for up to 12 months for BDI compared with placebo+MS.

Recurrence of Mania or Depression Among Adult Bipolar Patients Who Continued Using Lithium: A Single-group Summary Meta-analysis of Randomized Trials.

BACKGROUND: The exact recurrence rate of bipolar disorder in patients receiving lithium maintenance phase treatment and the modifiers associated with recurrence are still unknown. METHODS: We searched Embase, PubMed, and CENTRAL from inception until April 28, 2020. Outcomes included recurrence rate of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes; all-cause discontinuation rate; and discontinuation rate due to adverse events. A random-effects model, single-group summary meta-analysis was conducted. A meta-regression analysis to examine whether the modifiers (total number of patients, %female, mean age, duration of study, duration of preliminary phase, publication year, bipolar disorder type, mood status at recruitment, presence of a placebo arm, sponsorship, enrichment design, number of treatment arms, and risk of bias for blinding or randomization) were associated with the event rate of the outcomes was also performed. RESULTS: We identified 21 randomized trials (n = 1,415; mean study duration, 78.40 ± 32.10 weeks; %female, 54.85%; mean age, 43.47 ± 4.88 years). The event rates (95% confidence interval [CI]) were as follows: recurrence of any mood episode, 39.8% (32.8%, 47.1%); depressive episodes, 25.6% (18.8%, 34.0%); manic/hypomanic/mixed episodes, 18.5% (13.7%, 24.7%); all-cause discontinuation rate, 67.0% (57.2%, 75.5%); and discontinuation rate due to adverse events, 8.7% (5.1%, 14.7%). After adjusting for multiple testing, our meta-regression analysis showed association only between the all-cause discontinuation rate and presence of a placebo arm. CONCLUSIONS: The recurrence rate of depressive episodes seemed to be higher than the recurrence rate of manic/hypomanic/mixed episodes. The all-cause discontinuation rate was high. However, the studies included in our meta-analysis were of short duration.

Efficacy and Safety of Psychostimulants for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Several reports of the effectiveness of the use of psychostimulants for the treatment of Alzheimer's disease (AD) are available. METHODS: A systematic review and meta-analysis was conducted including double-blind, randomized, placebo-controlled trials. Outcomes were the improvement of apathy scales score (primary), mini-mental state examination (MMSE) score, activities of daily living scale score, Zarit burden interview score, all-cause discontinuation, discontinuation due to adverse events, and incidence of at least 1 adverse event. RESULTS: Three methylphenidate studies and 1 modafinil study were identified (n=156). Results from combined psychostimulants were superior to placebo in the improvement of apathy scales score (standardized mean differences [SMD]=-0.63 (-1.22, -0.04), p=0.04, all studies) and the MMSE score (SMD=-0.58 (-1.14, -0.02), p=0.04, 3 methylphenidate studies). The modafinil study was excluded from the meta-analysis for the improvement of apathy scales score; therefore, the effect size increased (SMD=-0.82 (-1.43, -0.20), p=0.009). However, no significant differences were observed in terms of other outcomes, including safety outcomes between the treatment groups. DISCUSSION: Methylphenidate would be effective in treating apathy and cognitive impairment in AD patients.

Blonanserin patch vs. Other Antipsychotics for Acute Schizophrenia: A Systematic Review of Double-blind, Randomized, Placebo-controlled, Phase 3 Trials in Japan.

INTRODUCTION: The use of the blonanserin patch (BLO-P) for schizophrenia treatment was approved in Japan in 2019. This systematic review of trials in Japan assessed the efficacy and safety profile of BLO-P compared with other antipsychotics. METHODS: The systematic review included 6-week, double-blind, randomized, placebo-controlled, phase 3 trials in Japan that included patients with acute schizophrenia. Pooled data for patients receiving BLO-P 40 and 80 mg/day (BLO-P40+80) were compared with pooled data for patients receiving asenapine 10 and 20 mg/day (ASE10+20) and data for those receiving brexpiprazole 2 mg/day (BRE2) and paliperidone extended-release 6 mg/day (PAL-ER6). RESULTS: All the investigated treatments were superior to placebo in reducing the Positive and Negative Syndrome Scale (PANSS) total score; the Hedges' g values (95% confidence interval) for BLO-P40+80, ASE10+20, BRE2, and PAL-ER6 were-0.40 (-0.58,-0.22),-0.61 (-0.79,-0.42),-0.33 (-0.60,-0.07), and-0.69 (-0.93,-0.45), respectively. There were differences among the antipsychotics in the incidence of various individual adverse events. DISCUSSION: BLO-P40+80 may have a good efficacy/safety/tolerability profile for the treatment of patients with acute schizophrenia.

Brexpiprazole as Adjunctive Treatment for Major Depressive Disorder Following Treatment Failure With at Least One Antidepressant in the Current Episode: a Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis included double-blind, randomized, placebo-controlled trials of brexpiprazole adjunctive treatment (0.5-3 mg/d) for major depressive disorder where antidepressant treatment had failed. METHODS: The outcomes were the response rate (primary), remission rate (secondary), Montgomery Åsberg Depression Rating Scale score (secondary), Sheehan Disability Scale scores (secondary), Clinical Global Impression-Improvement/Severity scores, discontinuation rate, and individual adverse events. A subgroup meta-analysis of the data at week 6 compared outcomes by dose >2 mg/d or ≤2 mg/d (2 mg/d is the recommended dose). RESULTS: We identified 9 studies (n = 3391). Compared with placebo, brexpiprazole (any dose) was superior for response rate (risk ratio [RR] = 0.93, 95% confidence interval [95% CI] = 0.89-0.97, number needed to treat = 17), remission rate (RR = 0.95, 95% CI = 0.93-0.98, number needed to treat = 25), Montgomery Åsberg Depression Rating Scale score (standardized mean difference = -0.20, 95% CI = -0.29, -0.11), Sheehan Disability Scale score (standardized mean difference = -0.12, 95% CI = -0.21, -0.04), and Clinical Global Impression-Improvement/Severity scores but was associated with a higher discontinuation rate, akathisia, insomnia, restlessness, somnolence, and weight increase. Doses >2 mg/d had a significantly higher RR for response rate than ≤2 mg/d (0.96 vs 0.89); moreover, compared with placebo, doses >2 mg/d were associated with higher incidences of akathisia (RR = 4.58) and somnolence (RR = 7.56) as well as were marginally associated with a higher incidence of weight increase (RR = 3.14, P = .06). Compared with placebo, doses ≤2 mg/d were associated with higher incidences of akathisia (RR = 2.28) and weight increase (RR = 4.50). CONCLUSIONS: Brexpiprazole adjunctive treatment is effective for major depressive disorder when antidepressant treatment fails. At 6 weeks, doses ≤2 mg/d presented a better risk/benefit balance than >2 mg/d.

Effect of discontinuation v. maintenance of antipsychotic medication on relapse rates in patients with remitted/stable first-episode psychosis: a meta-analysis.

BACKGROUND: Discontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance. METHODS: This meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18-24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model. RESULTS: Ten RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18-24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant). CONCLUSIONS: Maintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18-24 months) did not experience a relapse.

Relationship between VEGF-related gene polymorphisms and brain morphology in treatment-naïve patients with first-episode major depressive disorder.

Vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder (MDD). Recently, a genome-wide association study has revealed that four VEGF-related single nucleotide polymorphisms (SNPs) (i.e., rs4416670, rs6921438, rs6993770 and rs10738760) were independently associated with circulating VEGF levels. The current study investigated the relationship between brain volume and these four SNPs in first-episode drug-naïve MDD patients. A total of 38 first-episode drug-naïve MDD patients and 39 healthy subjects (HS) were recruited and underwent high-resolution T1-weighted imaging. Blood samples were collected from all the participants for serum VEGF assays and VEGF-related SNPs genotyping. Genotype-diagnosis interactions related to whole-brain cortical thickness and hippocampal subfield volumes were evaluated for the four SNPs. The results revealed a genotype-diagnosis interaction only for rs6921438 (i.e., the MDD patients and HS with the G/G genotype versus the MDD patients and HS with A-carrier genotype) in the subiculum of the left hippocampus (p < 0.05), and not the other SNPs. There was a volume reduction in the left subiculum of G/G genotype patients compared with the other groups. The "hypochondriasis" scores of the HAMD-17 scale were significantly higher in the G/G genotype patients than the A-carrier genotype patients. The association was observed between VEGF-related SNP rs6921438 and subiculum atrophy in first-episode drug-naïve MDD patients.

Efficacy, Tolerability, and Safety of Blonanserin in Schizophrenia: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: We conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing blonanserin with other antipsychotics (amisulpride, aripiprazole, haloperidol, paliperidone, and risperidone). METHODS: Weighted mean difference (WMD), risk ratio, and number needed to harm (NNH) with 95% confidence intervals (95% CIs) were calculated using random-effects model. RESULTS: Ten RCTs (n=1521) were included in this study. Blonanserin was superior to aripiprazole in improvement of Positive and Negative Syndrome Scale total scores (WMD=-10.62, 95% CI=-17.67 to -3.560, p=0.003). Blonanserin was associated with a higher incidence of all-cause discontinuation (RR=1.373, 95% CI=1.088-1.734, p=0.008, NNH=11), akathisia, extrapyramidal disorder, and agitation/excitement and a lower risk of hyperprolactinemia compared with risperidone + paliperidone. DISCUSSION: The current meta-analytic study did not update the comparison of blonanserin vs. haloperidol because there were no new RCTs. Our results suggest that the efficacy of blonanserin for schizophrenia is comparable with that of other antipsychotics, and blonanserin seems to be well tolerated.