People experiencing homelessness (PEH) attend emergency departments, often presenting with complex needs. The relationship between housing status and access to mental healthcare is not well established.

To compare characteristics, clinical severity and admission rates by housing status, and to examine whether homelessness is associated with admission after adjusting for severity.

We conducted a retrospective cohort study of patients referred to psychiatry at an inner-city emergency department between 1 January and 31 December 2020. Housing status was recorded at presentation. Severity was rated using the Threshold Assessment Grid (TAG, range 0–24). The primary outcome was hospital admission. Group differences were examined using t-tests and χ2 tests. Multivariable logistic regression models assessed variables associated with admission, adjusting for TAG total, age and gender, and then for individual TAG domains.

Of 771 referrals, 282 (36.6%) were PEH. PEH had higher severity (mean TAG 12.3 v. 8.1, p < 0.001) but lower admission rates (10.6 v. 18.0%, p = 0.006). All TAG domains were elevated among PEH, with the largest differences in survival, risk from others and social functioning. Each one-point TAG increase was associated with higher odds of admission (adjusted odds ratio (aOR) 1.34, p < 0.001), as was older age (aOR 1.04 per year, p < 0.001). PEH had lower odds of admission (aOR 0.16, p < 0.001), which persisted following domain-level adjustment (aOR 0.45, p = 0.039).

Despite greater severity, admission rates among PEH were lower following emergency psychiatric assessment. These findings highlight the need for better understanding of how emergency mental health services respond to the complex needs of this population.

Cariprazine is an atypical antipsychotic drug, demonstrating efficacy for the treatment of schizophrenia. This pharmacologic profile allows cariprazine to effectively treat the broad range of schizophrenia symptoms including positive symptoms (like delusions and hallucinations), negative symptoms (such as emotional withdrawal and social apathy), and cognitive impairments. A Phase IV, prospective, multi centre, single arm study was conducted to evaluate safety and efficacy of cariprazine in Indian patients with Schizophrenia.

The Safety and Efficacy of Cariprazine capsules was evaluated in the subset of patients with with schizophrenia.

Patients diagnosed with schizophrenia with or without psychotic symptoms at least 1 year prior, based on DSM-V criteria, were enrolled in the study with the Positive and Negative Syndrome Scale (PANSS) 80-120 (both inclusive). A total 97 patients, in the age range of 18 to 65 years, received Cariprazine starting dose 1.5 mg with further up titration to 3 to 6 mg for 6-weeks Primary Endpoint was safety evaluation and Secondary Endpoints were change PANSS score (total, positive subscale and negative subscale) Clinical global impression-Severity (CGI-S) score. [Clinical Trial Registration: [CTRI/2023/05/052793]

A total of 39 TEAEs were reported in 29, patients, Insomnia was the most common TEAE 12 events, followed by constipation, headache, sleep disorder, and night sweats (3 events each). All events were grade 1 (mild) and resolved.

With cariprazine treatment continued, there is gradual improvement in study patients based on PANSS total scores change (Mean±SD) constantly from Day 7 (-3.70 ±4.99) to Day 42 (-32.94 ±16.25). Similarly Positive and negative subscale scores (Mean±SD) were changed by Day 42 -9.79 ± 6.19 and -6.02 ± 4.30, respectively. CGI-S scores (Mean±SD) showed consistent improvement, decreasing from -0.20±0.40 at Day 7 to -1.55±1.02 at Day 42.

Cariprazine capsules demonstrated efficacy in managing the clinical symptoms of schizophrenia This drug may serve as a therapeutic option, potentially reducing symptom severity and enhancing overall mental well-being. The study treatment was found to be safe and well tolerated.

None Declared

Cariprazine is an atypical antipsychotic drug, demonstrating efficacy across manic, depressive, and mixed episodes in bipolar disorder with a favourable safety profile making it a good therapeutic option in patient management. A Phase IV, prospective, multi centre, single arm study was conducted to evaluate safety and efficacy of cariprazine in Indian patients with Schizophrenia and Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder.

The Safety and Efficacy of Cariprazine capsules was evaluated in the subset of patients with Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder in the Phase IV, single arm study.

Patients with Bipolar I disorder with, manic or mixed type, with or without psychotic symptoms, based on the DSM-V were enrolled in the study with Young Mania Rating Scale (YMRS) Total score ≥20 and Montgomery–Asberg Depression Rating Scale (MADRS) Total score <18. A total 75 patients, in the age range of 18 to 65 years, received Cariprazine starting dose 1.5 mg with further up titration to 3 to 6 mg for 3-weeks. Primary Endpoint was safety evaluation and secondary Endpoints were change in YMRS score, Clinical global impression -Bipolar version (CGI-BP) score and MADRS score. [Clinical Trial Registration: [CTRI/2023/05/052793]

A total of 15 TEAEs (Treatment emergent Adverse Events) were reported in 14 patients and insomnia (3 events) followed by, diarrhoea, vomiting, headache, and cough (2 events each) were most common. All events were grade 1 (mild) and resolved.

With cariprazine treatment continued, there is gradual improvement in study patients based on changes in YMRS CGI-BP, and MADRS scores. Mean (SD) change in YMRS scores were -9.97 (±6.76) on Day 21 (p<0.0001) demonstrating efficacy in alleviating manic symptoms. Mean (SD) changes in CGI-BP scores were -4.80 (±4.54) on Day 21 (p-values: <0.0001) leading to overall reduction in illness severity and improvement in global functioning. Mean (SD) changes in MADRS scores were -2.83 (±3.16) on Day 21 showing improvement in depressive symptoms and overall mood stabilization (p<0.0001).

Cariprazine capsules have demonstrated in managing clinical symptoms of Bipolar I disorder, with balanced efficacy in managing mania and bipolar depression in bipolar 1 disorder. The study treatment was found to be safe and well tolerated.

None Declared

Lumateperone, an atypical antipsychotic drug, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors.

This subgroup analysis of an Indian Phase 3 study was conducted to evaluate the efficacy and safety of Lumateperone 42mg compared to Quetiapine 300mg in treatment of Bipolar II depression when stratified based on age (18-45, >45-65).

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included Indian patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. The patients were stratified based on age: Subgroup 1 [S1]: 18-45 years and Subgroup 2 [S2]: >45-65 years. For efficacy outcomes MADRS score, CGI-BP-S (total score, depression subscore and overall bipolar illness subscore), and Quality of life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF) score were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This subgroup analysis included 462 patients, out of which 320 in S1[Test=159; Comparator=161] and 142 in S2[Test=72; Comparator=70]. The baseline demographic characteristics were comparable in between treatment arms across subgroups. The primary endpoint of reduction in MADRS score from baseline to Day 42 in Test arm was non-inferior to Comparator arm in both subgroups [Figure 1] as the upper 95% CI was below the pre-defined margin of 3.0. The reduction of CGI-BP-S (total score, depression subscore and overall bipolar illness subscore) from Day 14 to Day 42 were comparable in both Test and Comparator arms in both subgroups. The improvement in Q-LES-Q-SF score from baseline to Day 42 were comparable in both Test and Comparator arms in both subgroups. The incidence of TEAEs were comparable in both treatment arms [S1: Test=31.4% and Comparator=36.6%; S2: Test=41.7% and Comparator=32.9%] and no serious adverse events were reported.

Image 1:

This subgroup analysis demonstrated that Lumateperone 42mg is non-inferior to Quetiapine 300mg in treatment of Bipolar II depression as assessed via MADRS score from baseline to Day 42, irrespective of age of the patients and both treatments were found to be well tolerated. Hence, Lumateperone can be considered as valuable treatment option in management of Bipolar II depression.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma

Lumateperone, an atypical antipsychotic drug approved for Bipolar II depression in 2021, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors.

This subgroup analysis of an Indian Phase 3 study was conducted to evaluate the efficacy and safety of Lumateperone 42mg compared to Quetiapine 300mg in treatment of Bipolar II depression when stratified based on mixed symptoms assessed via Young Mania Rating Scale (YMRS).

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. The patients were stratified based on YMRS: Subgroup 1 [S1]: ≤6 and Subgroup 2 [S2]: >6 to 12. For efficacy outcomes MADRS score, CGI-BP-S (total score, depression subscore and overall bipolar illness subscore), and Quality of life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF) score were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This subgroup analysis included 235 patients in S1[Test=109; Comparator=126] and 227 in S2[Test=122; Comparator=105]. The baseline demographic characteristics were comparable in between treatment arms across subgroups. The primary endpoint of reduction in MADRS score from baseline to Day 42 in Test arm was non-inferior to Comparator arm in both subgroups [Figure 1] as the upper 95% CI was below the pre-defined margin of 3.0. The reduction of CGI-BP-S (total score, depression subscore and overall bipolar illness subscore) from Day 14 to Day 42 were comparable in both Test and Comparator arms in both subgroups. The improvement in Q-LES-Q-SF score from baseline to Day 42 were comparable in both Test and Comparator arms in both subgroups. The incidence of TEAEs were similar in both treatment arms [S1: Test=28.4% and Comparator=28.6%; S2: Test=40.2% and Comparator=43.8%] and no serious adverse events were reported.

Image 1:

This subgroup analysis demonstrated that Lumateperone 42mg is non-inferior to Quetiapine 300mg in treatment of Bipolar II depression as assessed via MADRS score from baseline to Day 42, irrespective of presence of mixed symptoms and both treatments were found to be well tolerated.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma.

Lumateperone, an atypical antipsychotic drug, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors.

This subgroup analysis of an Indian Phase 3 study was conducted to evaluate the efficacy and safety of Lumateperone 42mg compared to Quetiapine 300mg in treatment of Bipolar II depression when stratified based on disease duration.

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. The patients were stratified based on disease duration: Subgroup 1 [S1]: ≤6 months and Subgroup 2 [S2]: >6 months. For efficacy outcomes MADRS score, CGI-BP-S (total score, depression subscore and overall bipolar illness subscore), and Quality of life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF) score were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This subgroup analysis included 462 patients, out of which 118 in S1[Test=62; Comparator=56] and 344 in S2[Test=169; Comparator=175]. The baseline demographic characteristics were comparable in between treatment arms across subgroups. The primary endpoint of reduction in MADRS score from baseline to Day 42 in Test arm was non-inferior to Comparator arm in both subgroups [Figure 1] as the upper 95% CI was below the pre-defined margin of 3.0. The reduction of CGI-BP-S (total score, depression subscore and overall bipolar illness subscore) from Day 14 to Day 42 were comparable in both Test and Comparator arms in both subgroups. The improvement in Q-LES-Q-SF score from baseline to Day 42 were comparable in both Test and Comparator arms in both subgroups. The incidence of TEAEs were similar in both treatment arms [S1: Test=30.6% and Comparator=30.4%; S2: Test=36.1% and Comparator=37.1%] and no serious adverse events were reported.

Image 1:

This subgroup analysis demonstrated that Lumateperone 42mg is non-inferior to Quetiapine 300mg in treatment of Bipolar II depression as assessed via MADRS score from baseline to Day 42, irrespective of chronicity of the disease and both treatments were found to be well tolerated. Hence, Lumateperone can be considered as valuable treatment option in management of Bipolar II depression.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma.

Lumateperone, an atypical antipsychotic drug, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors.

This post-hoc analysis of an Indian Phase 3 study was conducted to evaluate the impact of Lumateperone 42mg compared to Quetiapine 300mg on severity of depression assessed via MADRS in patients with Bipolar II depression.

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. This post-hoc analysis evaluated MADRS total score and individual items from Question 1 to Question 10 i.e. (Q1) Apparent sadness; (Q2) Reported sadness; (Q3) Inner tension; (Q4) Reduced sleep; (Q5) Reduced appetite; (Q6) Concentration difficulties; (Q7) Lassitude; (Q8) Inability to feel; (Q9) Pessimistic thoughts; and (Q10) Suicidal thoughts respectively and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This subgroup analysis included 462 patients, out of which 231 were in the Test group and 231 in the comparator group. The baseline demographic characteristics were comparable in between treatment arms. The reduction in MADRS score (total and individual items) from baseline to Day 42 in Test arm was comparable to Comparator arm [Figure 1 & 2]. The incidence of TEAEs were similar in both treatment arms [Test: 34.6%; Comparator: 35.5%] and no serious adverse events were reported.

Image 1:

Image 2:

This post-hoc analysis demonstrated that Lumateperone 42mg is comparable to Quetiapine 300mg in treatment of Bipolar II depression as assessed via MADRS score from baseline to Day 42, and both treatments were found to be well tolerated. Hence, Lumateperone can be considered as valuable treatment option in management of Bipolar II depression.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma.

Lumateperone, an atypical antipsychotic drug approved in 2021 for bipolar depression, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors. In India, Quetiapine is one of the approved drugs for use in depressive episodes for bipolar disorder.

This post-hoc analysis of an Indian Phase 3 study was conducted to evaluate the correlation of severity of depression assessed via Montgomery-Asberg depression rating scale (MADRS) and severity of hypomania symptoms via Young Mania Rating Scale (YMRS) when treated with Lumateperone 42mg or Quetiapine 300mg.

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a MADRS score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. In this post-hoc analysis, correlation between MADRS and YMRS were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This post-hoc analysis included 462 patients [231 each in Test and Comparator]. The baseline demographic characteristics were comparable in between treatment arms. The Pearson’s correlation coefficient between change from baseline in MADRS score and YMRS score was statistically significant for both treatment arms at Day 42 [Test: 0.3144, p<0.0001; Comparator: 0.3284, p<0.0001] and the linear regression between 2 arms was not statistically significant (p=0.4203), indicating weak positive correlation between the 2 scales [Figure 1 and Figure 2]. The incidence of TEAEs were similar in both treatment arms [Test: 34.6%; Comparator: 35.5%] and no serious adverse events were reported.

Image 1:

Image 2:

This post-hoc analysis demonstrated that patients with Bipolar II depression when treated with Lumateperone 42mg or Quetiapine 300mg, the reduction in MADRS score is directly proportional to reduction in YMRS score and both treatments were well tolerated.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma

Lumateperone, an atypical antipsychotic drug approved in 2021 for bipolar depression, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors. In India, Quetiapine is one of the approved drugs for use in depressive episodes for bipolar disorder.

This post-hoc analysis of an Indian Phase 3 study was conducted to evaluate the correlation of severity of depression assessed via Montgomery-Asberg depression rating scale (MADRS) and quality of life assessed via Quality-of-life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF) when treated with Lumateperone 42mg or Quetiapine 300mg.

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a MADRS score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. In this post-hoc analysis, correlation between MADRS and Q-LES-Q-SF were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This post-hoc analysis included 462 patients [231 each in Test and Comparator]. The baseline demographic characteristics were comparable in between treatment arms. The Pearson’s correlation coefficient between change from baseline in MADRS score and Q-LES-Q-SF score was statistically significant for both treatment arms at Day 42 [Test: -0.192, p=0.0043; Comparator: -0.299, p<0.0001] and the linear regression between 2 arms was not statistically significant (p=0.0853), indicating weak negative correlation between the 2 scales [Figure 1 and Figure 2]. The incidence of TEAEs were similar in both treatment arms [Test: 34.6%; Comparator: 35.5%] and no serious adverse events were reported.

Image 1:

Image 2:

This post-hoc analysis demonstrated that patient with Bipolar II depression when treated with Lumateperone 42mg or Quetiapine 300mg, the reduction in MADRS score is inversely proportional to Q-LES-Q-SF score.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. G. Goyal: None Declared, S. Mangalwedhe: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, S. Saha Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma

Lumateperone, an atypical antipsychotic drug approved in 2021 for bipolar depression, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors. In India, Quetiapine is one of the approved drugs for use in depressive episodes for bipolar disorder.

This post-hoc analysis of an Indian Phase 3 study was conducted to evaluate the correlation of quality of life assessed via Quality-of-life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF) and severity of hypomania symptoms via Young Mania Rating Scale (YMRS) when treated with Lumateperone 42mg or Quetiapine 300mg.

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. In this post-hoc analysis, correlation between Q-LES-Q-SF and YMRS were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This post-hoc analysis included 462 patients [231 each in Test and Comparator]. The baseline demographic characteristics were comparable in between treatment arms. The Pearson’s correlation coefficient between Q-LES-Q-SF score and YMRS score was statistically significant for both treatment arms at Day 42 [Test: -0.268, p<0.0001; Comparator: -0.281, p<0.0001] and the linear regression between 2 arms was not statistically significant (p=0.8603), indicating weak negative correlation between the 2 scales [Figure 1 and Figure 2]. The incidence of TEAEs were similar in both treatment arms [Test: 34.6%; Comparator: 35.5%] and no serious adverse events were reported.

Image 1:

Image 2:

This post-hoc analysis demonstrated that patients with Bipolar II depression when treated with Lumateperone 42mg or Quetiapine 300mg, the improvement in Q-LES-Q-SF score is inversely proportional to YMRS score and both treatments were well tolerated.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma

Lumateperone, an atypical antipsychotic drug approved for Bipolar II depression in 2021, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors.

This post-hoc analysis of an Indian Phase 3 study was conducted to evaluate the impact of Lumateperone 42mg compared to Quetiapine 300mg on quality of life of patients with Bipolar II depression assessed via Quality-of-life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF).

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. This post-hoc analysis evaluated Q-LES-Q-SF total score and individual item scores [Physical health(1), Mood(2), Work(3), Household activities(4), Social relationships(5), Family relationships(6), Leisure time activities(7), Ability to function in daily life(8), Sexual drive, interest and/or performance(9), Economic status(10), Living/housing situation(11), Ability to get around physically(12), Ability to do work(13), Overall sense of wellbeing(14), and Overall life satisfaction and contentment(16)] for efficacy outcomes and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This post-hoc analysis included 462 patients [231 each in Test and Comparator]. The baseline demographic characteristics were comparable in between treatment arms. The improvement in Q-LES-Q-SF (total score and individual item scores) is significant from baseline to Day 42 in both treatment arms and comparable [Figure 1 and Figure 2 respectively]. Statistically significant improvement in Test over Comparator was observed for Item 7 (Leisure time activities) and Item 14 (Overall sense of wellbeing) [Figure 2]. The incidence of TEAEs were similar in both treatment arms [Test: 34.6%; Comparator: 35.5%] and no serious adverse events were reported.

Image 1:

Image 2:

This post-hoc analysis demonstrated that Lumateperone 42mg is comparable to Quetiapine 300mg in treatment of Bipolar II depression as assessed via Q-LES-Q-SF score from baseline to Day 42, and both treatments were found to be well tolerated.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma

Lumateperone, an atypical antipsychotic drug, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors.

This subgroup analysis of an Indian Phase 3 study was conducted to evaluate the efficacy and safety of Lumateperone 42mg compared to Quetiapine 300mg in treatment of Bipolar II depression when stratified based on baseline body mass index (BMI).

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. The patients were stratified based on baseline BMI: Subgroup 1 [S1]: <25Kg/m2 and Subgroup 2 [S2]: ≥25Kg/m2. For efficacy outcomes MADRS score, CGI-BP-S (total score, depression subscore and overall bipolar illness subscore), and Quality of life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF) score were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This subgroup analysis included 462 patients, out of which 276 in S1[Test=139; Comparator=137] and 186 in S2[Test=92; Comparator=94]. The baseline demographic characteristics were comparable in between treatment arms across subgroups. The primary endpoint of reduction in MADRS score from baseline to Day 42 in Test arm was non-inferior to Comparator arm in both subgroups [Figure 1] as the upper 95% CI was below the pre-defined margin of 3.0. The reduction of CGI-BP-S (total score, depression subscore and overall bipolar illness subscore) from Day 14 to Day 42 were comparable in both Test and Comparator arms in both subgroups. The improvement in Q-LES-Q-SF score from baseline to Day 42 were comparable in both Test and Comparator arms in both subgroups. The incidence of TEAEs were similar in both treatment arms [S1: Test=38.1% and Comparator=36.5%; S2: Test=29.3% and Comparator=34.0%] and no serious adverse events were reported.

Image 1:

This subgroup analysis demonstrated that Lumateperone 42mg is non-inferior to Quetiapine 300mg in treatment of Bipolar II depression as assessed via MADRS score from baseline to Day 42, irrespective of baseline BMI and both treatments were found to be well tolerated. Hence, Lumateperone can be considered as valuable treatment option in management of Bipolar II depression.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma

Lumateperone, an atypical antipsychotic drug, has a dual mechanism of action by combination of activity at central serotonin (5-HT2A) and dopamine (D2) receptors.

This subgroup analysis of an Indian Phase 3 study was conducted to evaluate the efficacy and safety of Lumateperone 42mg compared to Quetiapine 300mg in treatment of Bipolar II depression when stratified based on prior hypomanic episodes.

The phase-III, randomized, multi-centric, assessor-blind, parallel-group, active-controlled, comparative, non-inferiority study included Indian patients with Bipolar II depression with moderate severity having a Montgomery-Asberg depression rating scale (MADRS) score ≥20 and Clinical global impression–bipolar version–severity (CGI-BP-S) score ≥4. The study was conducted after receiving regulatory and ethics committee approvals. The patients were randomized (1:1) to either receive Lumateperone 42mg [Test] or Quetiapine 300mg [Comparator] for 6 weeks. The patients were stratified based on number of prior hypomanic episodes in lifetime: Subgroup 1 [S1]: 1 episode and Subgroup 2 [S2]: >1 episode. For efficacy outcomes MADRS score, CGI-BP-S (total score, depression subscore and overall bipolar illness subscore), and Quality of life enjoyment and satisfaction-short form questionnaire (Q-LES-Q-SF) score were evaluated and for safety outcomes treatment emergent adverse events (TEAEs) were assessed. [Clinical trial registration: CTRI/2023/10/058583]

This subgroup analysis included 462 patients, out of which 251 in S1[Test=129; Comparator=122] and 211 in S2[Test=102; Comparator=109]. The baseline demographic characteristics were comparable in between treatment arms across subgroups. The primary endpoint of reduction in MADRS score from baseline to Day 42 in Test arm was non-inferior to Comparator arm in both subgroups [Figure 1] as the upper 95% CI was below the pre-defined margin of 3.0. The reduction of CGI-BP-S (total score, depression subscore and overall bipolar illness subscore) from Day 14 to Day 42 were comparable in both Test and Comparator arms in both subgroups. The improvement in Q-LES-Q-SF score from baseline to Day 42 were comparable in both Test and Comparator arms in both subgroups. The incidence of TEAEs were similar in both treatment arms [S1: Test=37.2% and Comparator=35.2%; S2: Test=31.4% and Comparator=35.8%] and no serious adverse events were reported.

Image 1:

This subgroup analysis demonstrated that Lumateperone 42mg is non-inferior to Quetiapine 300mg in treatment of Bipolar II depression as assessed via MADRS score from baseline to Day 42, irrespective of number of previous hypomanic episodes and both treatments were found to be well tolerated.

A. Dharmadhikari: None Declared, P. Chaurasia: None Declared, Y. Patel: None Declared, D. Choudhary: None Declared, P. Dasud: None Declared, M. Bhirud: None Declared, P. Meena: None Declared, F. Shah: None Declared, G. Ganesan: None Declared, B. P. Rathour: None Declared, K. Mistry: None Declared, M. Dutta: None Declared, A. Ramaraju: None Declared, S. Mangalwedhe: None Declared, S. G. Goyal: None Declared, G. Kulkarni: None Declared, A. Mukhopadhyay: None Declared, P. Chaudhary: None Declared, G. T. Harsha: None Declared, M. Parikh: None Declared, S. Dey: None Declared, S. Sarkhel: None Declared, N. Jyothi: None Declared, A. Kumar: None Declared, N. Sooch: None Declared, A. Shetty Employee of: Sun Pharma, S. Saha Employee of: Sun Pharma, P. Devkare Employee of: Sun Pharma, A. Shetty Employee of: Sun Pharma, D. Patil Employee of: Sun Pharma, P. Ghadge Employee of: Sun Pharma, A. Mane Employee of: Sun Pharma, S. Mehta Employee of: Sun Pharma.

While biomarkers are widely used in other medical fields, psychiatry has yet to introduce reliable biological diagnostic tools. Female reproductive transitions provide a unique window of opportunity for investigating psychiatric biomarkers. Hormonal changes across menstruation, pregnancy, parturition and perimenopause can have dramatic effects on mental health in vulnerable individuals, enabling the identification of unique biomarkers associated with these fluctuations.

This review integrates current evidence concerning potential biomarkers, with focus on recent human studies in perinatal depression, anxiety and obsessive–compulsive disorder, postpartum psychosis, premenstrual dysphoric disorder and perimenopausal depression.

We identified potential articles to be included in this narrative review by using PubMed to obtain articles in English since 2010 on the six conditions listed above, with the additional keywords of ‘biomarker’, ‘epigenetics’, ‘neuroactive steroid’, ‘immune’, ‘inflammatory’ and ‘neuroimaging’.

There is substantial published evidence regarding potential biomarkers of reproductive psychiatric disorders in the areas of epigenetics, neuroactive steroids, immune function and neuroimaging. This body of research holds significant potential to advance biomarker development, uncover disease mechanisms and improve diagnostic and therapeutic strategies, but there is as yet no clinically useful biomarker in commercial development for any reproductive psychiatric disorder.

There is an urgent need for longitudinal, large-scale and multi-modal studies to examine potential biomarkers and better understand their functions across various stages of reproduction.

Motivated behaviors vary widely across individuals and are controlled by a range of environmental and intrinsic factors. However, due to a lack of objective measures, the role of intrinsic v. extrinsic control of motivation in psychiatric disorders remains poorly understood.

We developed a novel multi-factorial behavioral task that separates the distinct contributions of intrinsic v. extrinsic control, and determines their influence on motivation and outcome sensitivity in a range of contextual environments. We deployed this task in two independent cohorts (final in-person N = 181 and final online N = 258), including individuals with and without depression and anxiety disorders.

There was a significant interaction between group (controls, depression, anxiety) and control-condition (extrinsic, intrinsic) on motivation where participants with depression showed lower extrinsic motivation and participants with anxiety showed higher extrinsic motivation compared to controls, while intrinsic motivation was broadly similar across the groups. There was also a significant group-by-valence (rewards, losses) interaction, where participants with major depressive disorder showed lower motivation to avoid losses, but participants with anxiety showed higher motivation to avoid losses. Finally, there was a double-dissociation with anhedonic symptoms whereby anticipatory anhedonia was associated with reduced extrinsic motivation, whereas consummatory anhedonia was associated with lower sensitivity to outcomes that modulated intrinsic behavior. These findings were robustly replicated in the second independent cohort.

Together this work demonstrates the effects of intrinsic and extrinsic control on altering motivation and outcome sensitivity, and shows how depression, anhedonia, and anxiety may influence these biases.