Psychiatric randomised controlled trials increasingly privilege psychometric rating scales, yet bedside clinical training, remains the clinician's primary integrator of meaning, context, and change. Recent reconceptualisations describe clinical judgment as a three-stage process encompassing data collection through clinical interviewing, interpretationviaclinical reasoning, and decision making (Fava and Guidi, 2026; Fava et al., 2026). We provide a historically informed, conceptually focused analysis of the transition from narrative clinical impression to operationalised criteria and multi-item scales, and examine the emergence of clinician-judgment outcomes, particularly the Clinical Global Impressions (CGI) scales, as a hybrid bridge between these traditions. We argue that modern outcome assessment comprises two dominant families: multi-item symptom scales (e.g., PANSS, MADRS, HAM-A) and global clinician-judgment scales (CGI-Severity, CGI-Improvement). Global ratings can capture clinically salient information not fully represented by item totals, but only if their use preserves independent judgment. We propose "CGI 2.0": minimum standards for rater qualification, construct-focused training, structured justification, calibration/monitoring, and prespecified concordance/discordance analyses with primary symptom-scale endpoints, while cautioning against "industrialised" practices such as deriving CGI scores from multi-item totals. A clinimetric integration of psychometric methods that re-legitimises calibrated clinical judgment alongside rigorous measurement could improve interpretability, clinical relevance, and signal detection in psychopharmacology trials.

Abstract Background Anxious distress and mixed features are DSM-5 episode specifiers for major depressive episodes (MDE) associated with major depressive disorder (MDD) and bipolar disorder. Patients with depressive episodes with the specifiers have more severe symptoms, more comorbidities, increased suicide risk, and poorer treatment response than patients without the specifiers. Aims & Objectives Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. In a Phase 3, randomized, double-blind, placebo-controlled trial (Study 403; NCT04285515) lumateperone 42mg was efficacious over placebo with a favorable safety profile in patients with MDD or bipolar depression (BPD) with mixed features. This post hoc analysis of Study 403 investigated efficacy of lumateperone 42mg in patients with MDD or BPD with mixed features and anxious distress. Method Eligible adults (18-75 years) met DSM-5 criteria for an MDE with mixed features and had MDD, bipolar I, or bipolar II disorder, with Montgomery-Å sberg Depression Rating Scale [MADRS] Total score>=24 and Clinical Global Impression Scale-Severity [CGI-S] score>=4. Patients were stratified by MDD or bipolar disorder diagnosis and randomized 1:1 to 6-weeks lumateperone 42mg or placebo. This analysis evaluated patients with mixed features and DSM-5 anxious distress in the overall population (combined MDD/BPD) and separately in MDD and BPD individual populations. Assessments included change from baseline in MADRS Total score, CGI-S score, and MADRS inner tension item score. Results Of 383 patients in the combined MDD/BPD modified intent to treat (mITT) population with mixed features, 244 (63.7% of mITT; placebo, 121; lumateperone, 123) had anxious distress. Anxious distress was common in patients with MDD (73.9% of MDD mITT; placebo, 69; lumateperone, 67) and BPD (54.3% of BPD mITT; placebo, 52; lumateperone, 56). Compared with placebo, lumateperone significantly improved change from baseline for MADRS Total score at Day 43 in all 3 populations with anxious distress: combined MDD/BPD population (least squares mean difference vs placebo [LSMD], −6.1; 95% CI −8.52 to −3.71; effect size [ES], −0.67; P<.0001), MDD individual population (LSMD, −6.8; 95% CI −9.82 to −3.77; ES, −0.79; P<.0001), and BPD individual population (LSMD, −5.5; 95% CI −9.34 to −1.62; ES, −0.59; P<.01). In all 3 populations, significantly greater (P <.05) reductions in change from baseline of MADRS Total score occurred by Day 15 and persisted throughout the study in lumateperone-treated patients. Similarly, lumateperone significantly improved change from baseline for CGI-S score at Day 43 vs placebo for patients with anxious distress in the combined MDD/BPD population (LSMD, −0.5; 95% CI −0.78 to −0.26; ES, −0.54; P<.0001), MDD individual population (LSMD, −0.6; 95% CI −0.98 to −0.30; ES, −0.66; P<.001), and BPD individual population (LSMD, −0.4; 95% CI −0.82 to −0.05; ES, −0.48; P<.05). Lumateperone also significantly improved change from baseline for the inner tension MADRS single-item score at Day 43 compared with placebo for all 3 populations (P<.05). Discussion & Conclusion Lumateperone 42mg demonstrated efficacy in improving symptoms of major depression with mixed features and anxious distress, including global disease severity and inner tension, in patients with MDD or bipolar disorder.

This study employs artificial intelligence methods to predict mood phases in patients with bipolar disorder, addressing the issue of poor prognosis caused by recurrent episodes and uncertainty in mood phases. To explore the patterns of mood transitions in patients with bipolar disorder, we developed a mood phase transition model using a Transformer model to investigate whether predicting mood changes can improve prognosis. We conducted cohort follow-up assessments of patients with bipolar disorder. At each visit, patients were evaluated using the Hamilton Depression Rating Scale (HAMD) and the Young Mania Rating Scale (YMRS) as clinician-rated assessments, along with the BDCC self-rating scale. We then input these data into several different AI models for training and validated the models’ performance using the data. The study was conducted through online medical platforms and offline follow-up evaluations. The study included 812 patients diagnosed with bipolar disorder according to DSM-5 criteria, who had at least one BDCC assessment result and at least one depressive episode meeting HAMD criteria and one manic/hypomanic episode meeting YMRS criteria. In the experiment utilizing current self-assessment scales for rapid identification of affective states, the best performance was observed with the Transformer and RF models, with AUCs for affective state identification of 0.83 (95 http://ClinicalTrials.gov under the identifier NCT02015143

Objective: To assess the efficacy of cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, as adjunctive treatment for patients with major depressive disorder (MDD) and inadequate response to ongoing antidepressant therapy (ADT).Methods: This randomized, double-blind, placebo-controlled study was conducted from November 2018 to September 2021. Adults with MDD per DSM-5 criteria were randomized (1:1:1) to cariprazine 1.5 mg/d or 3 mg/d plus ADT, or placebo plus ADT. The primary and secondary endpoints were change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score and Clinical Global Impressions-Severity of Illness (CGI-S) score, respectively.Results: A total of 249 placebo-, 250 cariprazine 1.5 mg/d-, and 251 cariprazine 3 mg/d-treated patients were included in the modified intent-to-treat population. At week 6, the least squares mean change in MADRS total score was -13.8 for cariprazine 1.5 mg/d, -14.8 for cariprazine 3 mg/d, and -13.4 for placebo; differences versus placebo were not statistically significant. Mean change from baseline in CGI-S scores at week 6 was not significant for cariprazine versus placebo, although a trend toward significance was observed for 3 mg/d (P = .0573 [not adjusted for multiplicity]). Common treatment-emergent adverse events (≥ 5% either cariprazine group and twice placebo) were akathisia and insomnia.Conclusions: There were no statistically significant differences for cariprazine 1.5 or 3 mg/d versus placebo on the primary or secondary outcomes. Cariprazine was generally well tolerated, and no new safety concerns were detected.Clinical Trials Registration: ClinicalTrials.gov identifier NCT03739203.

Abstract Background Patients with major depressive disorder (MDD) often do not respond to antidepressant (ADT) monotherapy; adjunctive treatment is often used to address this unmet need. Cariprazine (CAR), a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with manic, mixed, or depressive episodes of bipolar I disorder, is under investigation as adjunctive therapy for patients with MDD. Methods This randomized, double-blind, phase 3 placebo (PBO)-controlled study assessed the efficacy, safety, and tolerability of CAR 1.5 and 3 mg/d as an adjunct to ADT in adult patients with MDD (18–65 years) and inadequate response to ADT alone (NCT03738215). The primary endpoint was change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impressions (CGI) were also assessed. Treatment response was defined as at least 50% decrease in MADRS total score at week 6. Results Patients (n=751) in the modified intent-to-treat population were randomly assigned to CAR 1.5 mg/d+ADT (n=250), CAR 3 mg/d+ADT (n=252), or PBO+ADT (n=249). Mean age was 44.8 years and 73.4% were female; mean baseline total scores were: MADRS=32.5, HAMD-17=25.9, HAM-A= 21.4. Overall, 89.7% of patients completed the study; rates of discontinuation due to adverse events (AEs) and lack of efficacy were 3.6% and 0.5%, respectively. The difference in MADRS total score change from baseline to week 6 was statistically significant after multiplicity adjustment for CAR 1.5 mg/d vs PBO (-14.1 vs -11.5; adjusted P=.0050), but not for CAR 3 mg/d (-13.1; P=.0727). Differences for CAR 1.5 mg/d vs PBO were observed by week 2 (nominal P=.0453) and maintained at weeks 4 (nominal P<.0001) and 6 (nominal P=.0025). At week 6, more CAR 1.5 mg/d patients (44%) than PBO patients (34.9%) responded to treatment (nominal P=.0446). Greater improvement in the CGI-I scores was observed for CAR 1.5 (nominal P=.0026) and 3 mg/d (nominal P=.0076) vs PBO. At week 6, improvement in HAMD-17 total score reached nominal significance for CAR 1.5 mg/d vs PBO (-13.1 vs -11.1; nominal P=.0017), but not for CAR 3 mg/day (-12.2; P=.0783). HAM-A improvement was greater for CAR 1.5 mg/d vs PBO (nominal P=.0370). There were no deaths; 2 serious AEs occurred in each group (CAR: kidney infection, social stay hospitalization; PBO: depression, multiple sclerosis). The most common CAR AEs (≥5% and twice PBO) were akathisia and nausea. Conclusion Cariprazine 1.5 mg/d was effective as adjunctive treatment in adults with MDD and inadequate response to ADT. Cariprazine was generally well tolerated, with a safety profile that was consistent with other indications. Together with results from a prior flex-dose study, these results suggest that adjunctive cariprazine may be an effective option for patients with inadequate response to ADT alone. Funding AbbVie

OBJECTIVE:The purpose of this study was to investigate the efficacy of cariprazine, a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist, as adjunctive therapy for patients with major depressive disorder and nonresponse to at least one antidepressant monotherapy.METHODS:In this double-blind placebo-controlled study, adults with major depressive disorder and inadequate response to antidepressants alone were randomized in a 1:1:1 ratio to placebo, cariprazine at 1.5 mg/day, or cariprazine at 3.0 mg/day. The primary outcome was change from baseline to week 6 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS). Least-squares mean differences were estimated in the modified intent-to-treat (mITT) population using a mixed-effects model for repeated measures with adjustment for multiple comparisons.RESULTS:The mITT population comprised 751 patients (placebo: N=249; cariprazine 1.5 mg/day: N=250; cariprazine 3.0 mg/day: N=252). At week 6, the mean reduction from baseline in MADRS total score was significantly greater with cariprazine 1.5 mg/day than with placebo (-14.1 vs. -11.5) but not with cariprazine 3.0 mg/day (-13.1). Significant differences between the cariprazine 1.5 mg/day and placebo groups were also observed at weeks 2 and 4. Meeting the MADRS response criteria was significantly more likely among patients receiving cariprazine 1.5 mg/day than placebo (44.0% vs. 34.9%); remission rates were not significantly different among groups. Common treatment-emergent adverse events (≥5% in either cariprazine group and twice the placebo rate) were akathisia and nausea.CONCLUSIONS:Adjunctive cariprazine at 1.5 mg/day demonstrated efficacy in reducing depressive symptoms in adults with major depressive disorder and inadequate response to antidepressants alone. Cariprazine was generally well tolerated, with a safety profile that was consistent with previous findings.

Back to table of contents Previous article Next article Letters to the EditorNo AccessTreatments for Depression in Bipolar II DisorderSuresh Durgam, M.D., Richard Chen, Ph.D., Joseph R. Calabrese, M.D., Gary S. Sachs, M.D.Suresh DurgamSearch for more papers by this author, M.D., Richard ChenSearch for more papers by this author, Ph.D., Joseph R. CalabreseSearch for more papers by this author, M.D., Gary S. SachsSearch for more papers by this author, M.D.Published Online:1 Sep 2022https://doi.org/10.1176/appi.ajp.22010081AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View article Access content To read the fulltext, please use one of the options below to sign in or purchase access. Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byNone Volume 179Issue 9 September 2022Pages 688-690 Metrics KeywordsBipolar and Related DisordersBipolar II DisorderClinical Drug StudiesPharmacotherapyAntipsychoticsSecond GenerationPDF download History Received 27 January 2022 Accepted 21 March 2022 Published online 1 September 2022 Published in print 1 September 2022

Over his long and distinguished career, Charles Bowden, MD, was a tireless advocate for bipolar disorder patients and an inspiration to colleagues. Trisha Suppes and Gary Sachs reflect on Bowden’s contributions to the field.

Background: Brexpiprazole is a dopamine/serotonin receptor partial agonist (D2, 5-HT1A) and antagonist (5-HT2A) approved for treatment of schizophrenia and major depressive disorder (adjunct to antidepressants). Aims: This study aimed to investigate brexpiprazole as monotherapy in acute mania (bipolar I disorder) in two short-term (ST) studies (study 080 and study 081) and one open-label (OL) extension (study 083). Methods: ST studies were three-week randomized, double-blind, flexible dose (2–4 mg/day), placebo-controlled studies. The primary endpoint was mean change in Young Mania Rating Scale (YMRS) total score from baseline to day 21. The OL study was a 26-week flexible dose (2–4 mg/day) study for patients completing the ST studies. Results: A total of 164 and 158 (study 080) and 170 and 162 (study 081) inpatients with DSM-5 mania with/without mixed features were randomized to placebo or brexpiprazole, respectively. The primary analyses did not show a statistically significant difference between brexpiprazole and placebo: study 080: least squares mean difference (95% confidence limits): 0.14 (−1.74, 2.03), p = 0.8797; study 081: −1.62 (−3.56, 0.32), p = 0.1011. OL study patients (n = 381) demonstrated a gradual improvement in YMRS total score. Akathisia was the only adverse event, with an incidence of ⩾5% with brexpiprazole and more than placebo in the ST studies, or ⩾5% in the OL study. Brexpiprazole was more efficacious in patients with impaired or no insight (predominantly EU patients) than in patients with excellent insight (predominantly US patients). Conclusions: Further studies are necessary to address the potential efficacy of brexpiprazole in acute mania, which should ensure that the study sample is severe enough (especially with regard to insight), and that the dose/titration schedule is not too modest.

OBJECTIVE:In a phase 3 randomized double-blind placebo-controlled study, the authors investigated the efficacy and safety of 42 mg/day of lumateperone in patients with bipolar I or bipolar II disorder experiencing a major depressive episode.METHODS:Patients 18-75 years old with a clinical diagnosis of bipolar I or bipolar II disorder and experiencing a major depressive episode were eligible for the study. Patients were randomized in a 1:1 ratio to receive 42 mg/day of lumateperone (N=188) or placebo (N=189), administered orally once daily in the evening for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to day 43 in score on the Montgomery-Åsberg Depression Rating Scale (MADRS) and total score on the Clinical Global Impressions Scale-Bipolar Version severity scale (CGI-BP-S), respectively. Safety assessments included treatment-emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms, and suicidality.RESULTS:At day 43, lumateperone treatment was associated with significantly greater improvement from baseline in MADRS score compared with placebo (least squares mean difference compared with placebo, -4.6 points; effect size=-0.56) and CGI-BP-S total score (least squares mean difference compared with placebo, -0.9; effect size=-0.46). Significant MADRS superiority for lumateperone over placebo was observed both in patients with bipolar I and bipolar II disorders. Somnolence and nausea were the only treatment-emergent adverse events that occurred with lumateperone at a clinically meaningful greater rate than placebo. The incidence of extrapyramidal symptom-related treatment-emergent adverse events was low and similar to that for placebo. Minimal changes were observed in weight, vital signs, or metabolic or endocrine assessments.CONCLUSIONS:Lumateperone at 42 mg/day significantly improved depression symptoms and was generally well tolerated in patients with major depressive episodes associated with both bipolar I and bipolar II disorders.

OBJECTIVE:To evaluate the literature comparing antidepressant effects of multiple daily dosing versus single daily dosing of antidepressants.METHOD:Studies comparing efficacy of single versus multiple daily dosing of antidepressants were reviewed. Data from the clinical trials meeting our inclusion criteria was subgrouped according to the half-life of the antidepressant drug studied. Meta-analyses were carried out to compare antidepressant efficacy of single versus multiple daily dosing overall and separately for the short, intermediate, and long half life antidepressant agent subgroups.RESULTS:The review process identified 22 studies comparing the therapeutic effect of antidepressants according to their dosing schedules. Although most studies used antidepressant medications with short half-lives, none found a significant difference in therapeutic efficacy. Furthermore, the improvement rates in depression scores in between the two groups were almost identical (SDD versus MDD).CONCLUSION:This meta-analytic approach found no advantage for multiple daily dosing and suggests that sustained therapeutic serum levels are not necessary for achievement of therapeutic activity. Antidepressant benefit may simply require a limited duration of exposure above the threshold serum level. Administration of antidepressants in single daily doses appears sufficient to perturb the physiological pathways associated with depression sufficiently to achieve an adaptive therapeutic response. Moreover, a single daily dosing regimen offers the potential advantages of simplicity, increased compliance, and reduced adverse effects, which in turn would increase the overall success rate in treatment of depression.

OBJECTIVE:Cariprazine, a dopamine D3/D2 and 5-HT1A receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression. METHODS:In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1.5 mg/day (N=157) or 3.0 mg/day (N=165). The primary and secondary efficacy parameters were changes from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) score and Clinical Global Impressions severity (CGI-S) score, respectively. Least squares mean differences were estimated using a mixed model for repeated measures, and p values were adjusted for multiplicity. RESULTS:Both dosages of cariprazine were significantly more effective than placebo in improving depressive symptoms (reducing MADRS total score); the least squares mean differences were -2.5 (95% CI=-4.6, -0.4) for cariprazine at 1.5 mg/day and -3.0 (95% CI=-5.1, -0.9) for cariprazine at 3.0 mg/day. Both cariprazine dosages were associated with lower CGI-S scores compared with placebo, but the differences did not reach statistical significance after adjustment for multiplicity (least squares mean difference, -0.2 [95% CI=-0.5, 0.0] for the 1.5 mg/day group and -0.3 [95% CI=-0.5, 0.0] for the 3.0 mg/day group). Common treatment-emergent adverse events (in at least 5% of participants in either cariprazine treatment group and twice the rate of the placebo group) were nausea, akathisia, dizziness, and sedation. Mean changes in weight and metabolic parameters were relatively small and comparable across groups. CONCLUSIONS:Cariprazine, at both 1.5 mg/day and 3.0 mg/day, was effective, generally well tolerated, and relatively safe in reducing depressive symptoms in adults with bipolar I depression.

Objective: To evaluate patient-reported determinants of treatment effectiveness and tolerability amongst persons with major depressive or bipolar disorders. Methods: The Depression and Bipolar Support Alliance (DBSA) conducted an online survey February 2016-April 2016 asking participants about which outcomes are most important in determining subjective treatment effectiveness and tolerability. Results: In total, 896 participants completed the survey [49.9% unipolar depression (n = 447) and 50.1% bipolar depression (n = 449)]. Survey respondents reported several previous medication trials with the minority (25% of depression and 29% of bipolar group) of respondents reporting that their current treatment plan was completely effective. When asked how they know that the treatment is working, for both groups, the highest rated response was, "I don't feel overly anxious, agitated or irritable." Weight gain was the adverse effect that most commonly led respondents to discontinue a medication. Lethargy, emotional blunting, shaking/trembling and anxiety were also identified as common treatment-emergent experiences leading to medication discontinuation in greater than one-third of respondents. The bipolar group more frequently identified several signs that suggested treatment was working (e.g., improved neurocognitive function, improved sleep), as well as more frequently reported several reasons to discontinue medications (e.g., weight gain, trembling). Conclusion: Numerous factors emerged as important to patients when evaluating treatment effectiveness and tolerability. Some of these factors are inadequately assessed by current standard clinical trial outcome measures. Considering these important patient-centred outcomes in future clinical trials, treatment guidelines and direct patient care may serve to improve patient satisfaction, quality of life and the therapeutic alliance.

Bipolar disorder (BD) is a mood disorder characterized by recurrent episodes of depression and mania/hypomania. Depressive relapse in BD reach rates close to 50% in 1 year and 70% in up to 4 years of treatment. Several studies have been developed to discover more efficient treatments for BD and prevent relapses. However, most of relapse studies used only statistical methods. We aim to analyze the performance of machine learning algorithms in predicting depressive relapse using only clinical data from patients. Five well-used machine learning algorithms (Support Vector Machines, Random Forests, Naïve Bayes and Multilayer Perceptron) were applied to the Systematic Treatment Enhancement Program for Bipolar Disorder (STEPBD) dataset of a cohort of 800 patients who became euthymic during the study and were followed up for 1 year: 507 presented a depressive relapse and 293 did not. The algorithms showed reasonable performance in the prediction task, ranging from 61% to 80% in the F-measure. Random Forest algorithm had a higher average of performance (Relapse Group 68%; No Relapse Group 74%), although, the performance between classifiers showed no significant difference. Random Forest analysis demonstrated that the three most important mood symptoms observed were: interest, depression mood and energy. Results show that the machine learning algorithms could be seen as a sensible approach to better support medical decision-making in the BD treatment and prevention of future relapses.

Bipolar Disorder (BD) is characterized by mood changes that manifest as depressive episodes alternating with episodes of euphoria, in varying degrees of intensity. Women with BD may experience worsening symptoms during events of their reproductive life, particularly those suffering from Premenstrual Dysphoric Disorder (PMDD). The presence of PMDD in the diagnoses of BD is considered a marker of severity for the disease. In this study, data from a cohort of 1099 women with BD were used for an exploratory analysis using association rules in order to find associations between PMDD and BD symptoms. Of the thousands of generated rules, those that have associations with PMDD were selected and categorized, with confidence levels between 70% and 100%.

BACKGROUND:The majority of research in mood disorders has focused on pharmacologic, psychotherapeutic, and brain stimulation interventions. Conversely, the utility of less structured interventions, such as lifestyle modifications or wellness strategies, has remained understudied. The objective of the current study is to evaluate the frequency of use and perceived helpfulness of wellness strategies for bipolar and unipolar depression. METHODS:The Depression and Bipolar Support Alliance (DBSA) conducted an online survey asking participants about the use and helpfulness of wellness strategies. RESULTS:In total, 896 participants completed the survey (unipolar depression [n = 447] and bipolar depression [n = 449]). Wellness strategies were used by 62% and 59% of individuals with bipolar and unipolar depression, respectively. Listening to music, socializing, and adequate sleep were commonly reported wellness strategies. The majority of participants reported wellness strategies to be helpful. Use of wellness strategies was associated with greater overall perceived treatment effectiveness (P < .0001) and greater subjective helpfulness of medications (P = .039), psychotherapy (P < .0001), and peer support groups (P < .0001). CONCLUSIONS:Wellness strategies were commonly used by the majority of respondents. These strategies were subjectively helpful for most respondents and were associated with greater overall treatment effectiveness and increased helpfulness of medications, psychotherapy, and peer support groups. As such, wellness strategies should be considered while developing a holistic treatment plan for depression. Further research is needed to evaluate the antidepressant effects of specific wellness strategies to better understand the role of these interventions in the management of depression.