Cariprazine for treating psychosis: an updated meta-analysis.

PURPOSE: Early treatment of psychotic illness improves outcomes, reduces relapse rates and should not be delayed. Cariprazine is a promising antipsychotic drug and may be a valuable resource when clinicians are in doubt if psychotic symptoms are due to schizophrenia or bipolar disorder. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis that included seven studies (n = 2896) analyzing the effect of cariprazine in psychotic symptoms assessed by the positive and negative symptoms scale (PANSS). RESULTS: We found cariprazine to be significantly superior to placebo (Hedges' g = 0.40; 95% CI 0.32-0.49) for acute psychosis independently of primary psychiatric diagnosis and also to be superior to placebo for both schizophrenia (Hedges' g = 0.39; 95% CI 0.29-0.50) and bipolar patients (Hedges' g = 0.43; 95% CI 0.27-0.58). CONCLUSIONS: We propose that cariprazine may be useful in treating psychosis independently of nosological differentiation at the beginning of the treatment Key pointsEarly treatment of psychotic illness with antipsychotic medications improves outcomes and reduces relapse rates.Cariprazine was found to be significantly superior to placebo for acute psychosis independently of primary psychiatric diagnosis.Cariprazine may be useful in treating psychosis independently of nosological differentiation between schizophrenia and bipolar disorder at the beginning of the treatment.

Effect of a 10-day transcutaneous trigeminal nerve stimulation (TNS) protocol for depression amelioration: A randomized, double blind, and sham-controlled phase II clinical trial.

BACKGROUND: Major depressive disorder (MDD) is one of the leading causes of disability in the world. However, treatment options are still limited, and marked by high refractoriness rates, new approaches are needed to optimize clinical improvement. Trigeminal nerve stimulation (TNS) is an innovative neuromodulation strategy consisting on the application of an electric current over the trigeminal nerve that propagates stimuli towards brain areas involved in mood control. OBJECTIVE: We examined the effects of TNS in MDD after a 10-day experimental protocol. METHODS: This was a randomized, double blind, and sham-controlled phase II study with 24 patients with severe MDD. Patients underwent a 10-day intervention protocol and were assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) at following three observation points: baseline (T1), after 10 days (T2), and after one month of the last stimulation session (T3). Main clinical outcome analysis of variance (ANOVA) was performed. RESULTS: Patients in the active group presented a mean reduction of 36.15% in depressive symptoms after the stimulation protocol. There was a significant interaction between group and time regarding HDRS-17 scores (F = 3.18; df = 2; p = 0.0456). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms at T2 (p = 0.040) and T3 (p = 0.026), which highlights the sustained amelioration of depressive symptoms. CONCLUSION: The present study found amelioration of depressive symptoms for patients undergoing a 10-day stimulation protocol of TNS, and this was sustained after one month of follow-up.

Effect of a 10-day trigeminal nerve stimulation (TNS) protocol for treating major depressive disorder: a phase II, sham-controlled, randomized clinical trial.

BACKGROUND: Considering both the burden determined by major depressive disorder (MDD) itself and the high refractoriness and recurrence index, alternative strategies, such as trigeminal nerve stimulation (TNS), are the cutting edge instruments to optimize clinical response and to avoid treatment discontinuation and relapse of symptoms. Trigeminal nerve stimulation is an incipient simple, low-cost interventional strategy based on the application of an electric current over a branch of the trigeminal nerve with further propagation of the stimuli towards brain areas related to mood symptoms. METHOD: The study was a phase II, randomized, sham-controlled trial with 40 patients with MDD. Patients with moderate or severe depressive symptoms as assessed by adequate clinical scales underwent a 10-day intervention protocol. Regarding main clinical outcome, analysis of variance (ANOVA) was performed to evaluate mean change scores in depressive symptoms as assessed by the HDRS-17 between baseline (t1), after intervention protocol (t2), and during one-month follow-up (t3). RESULTS: There was a significant interaction between the mean percentage changes in depressive symptoms according to the HDRS in the two groups across the three assessments (F=6.38, df=2, p=0.0033). Post hoc analyses (Bonferroni method) demonstrated a statistically significant difference between depressive symptoms at baseline and t1 (p=0.01) and between depressive symptoms at baseline and t2 (p=0.009). No severe adverse effects were reported. DISCUSSION: Our results in the present controlled trial highlight the possibility of more practical treatment protocols for clinical research, which are similar to those for different neuromodulation strategies such as transcranial direct current stimulation (tDCS). The in-office administration of TNS in our protocol is similar to the schedule for repetitive transcranial magnetic stimulation (rTMS), though over fewer treatment sessions. CONCLUSION: Further controlled studies will contribute to the establishment of the clinical relevance of this new treatment strategy for MDD.

Randomized clinical trial on the efficacy of a new transcranial direct current stimulation (tDCS) device in the treatment of depression: a low-cost option for developing countries? / Ensaio clínico randomizado sobre a eficácia de novo equipamento de estimulação transcraniana por corrente contínua (ETCC) no tratamento da depressão: uma opção de baixo custo para países em desenvolvimento?

ABSTRACT Objective: Verify the clinical efficacy and safety of a low-cost tDCS device, in a clinical trial for major depressive disorder. Methods: 168 persons were recruited; 32 depressed individuals with moderate or severe depressive symptoms (HDRS17 scores higher than 18) were included and randomized for the trial (16 individuals in each group). The intervention consisted of 10 active anodal tDCS sessions at 2 mA for 30 minutes over the left dorsolateral prefrontal cortex; or sham. The main outcome was HDRS17; secondary outcomes included satisfaction (TSQM II) and quality of life (WHOQOL-BREF). Assessments at baseline, endpoint and at 30 days follow-up. Results: The sample was composed by a total of 11 men and 21 women, mean age of 42.75 years (95% CI: 38.10-47.40). Active treatment was superior than sham: There was a significant interaction between group and time regarding HDRS-17 scores (F = 4.089, df = 2, p = 0.029; partial Eta squared = 0. 239). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms after a 30 days follow-up (difference = -7.75, p = 0.008, Cohen's d = 1.069). There were 3 dropouts, all in the active group, due schedule issues. No severe adverse effects reported. Conclusion: The current active tDCS protocol was related with clinical improvement of depressive symptoms. Intervention was well-tolerated. Non-invasive brain stimulation techniques are still not routinely used, although a viable strategy for treatment-resistant patients, partial responders and people unable to use pharmacological treatment. We aim to increase knowledge and use of tDCS for the Brazilian population.

RESUMO Objetivo: Testar a eficácia clínica e a segurança de equipamento de estimulação elétrica transcraniana por corrente contínua (ETCC) de baixo custo em ensaio clínico para transtorno depressivo maior (TDM). Métodos: Foram recrutadas 168 pessoas e incluídos e randomizados 32 indivíduos com depressão moderada ou grave (escores na HDRS17 >18; 16 indivíduos em cada grupo). A intervenção consistiu de 10 sessões de ETCC ativa a 2 mA no córtex pré-frontal dorsolateral esquerdo por 30 minutos, ou sham. O desfecho principal foi HDRS17; os desfechos secundários foram satisfação (TSQM II) e qualidade de vida (WHOQOL-BREF). Avaliações no início, no final do tratamento e após 30 dias de seguimento. Resultados: A amostra foi composta de 11 homens e 21 mulheres, com idade média de 42,75 anos (IC 95%: 38,10 a 47,40). O tratamento ativo foi superior ao sham: houve interação significativa entre grupo e tempo em relação aos escores de HDRS17 na ANOVA (F = 4,089, df = 2, p = 0,029; partial Eta squared = 0,239). A análise post hoc mostrou diferença significativa na HDRS17 no follow-up após 30 dias (diferença = -7,75, p= 0,008, Cohen's d = 1,069). Houve 3 dropouts, todos no grupo ativo, devido a problemas de agenda. Não houve registro de efeitos adversos graves. Conclusão: O tratamento ativo teve relação com melhora clínica de sintomas depressivos. A intervenção foi bem tolerada. Técnicas de estimulação cerebral não invasivas ainda não são rotina na prática clínica, apesar de estratégias viáveis para pacientes resistentes a tratamento, respondedores parciais e pessoas com intolerância a medicamentos. Esperamos ampliar o conhecimento e o uso de protocolos de ETCC na população brasileira.