The cross-sectional relationship among omega-3 fatty acid levels, cardiorespiratory fitness, and depressive symptoms from the Cooper Center Longitudinal Study.

OBJECTIVE: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are implicated in numerous illnesses including depression. The literature is mixed regarding the relationship between n-3 PUFA levels and depression, and studies based on self-reported dietary n-3 PUFA intake may not accurately reflect in vivo levels. METHOD: The current cross-sectional analysis examined the relationship between erythrocyte levels (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CESD), adjusting for health-related factors and omega-3 supplement use in 16,398 adults assessed at the Cooper Clinic in Dallas, Texas for preventative medical examinations between April 6, 2009, and September 1, 2020. A three-stage hierarchical linear regression was conducted to examine the EPA and DHA levels on CES-D before and after inclusion of cardiorespiratory fitness (CRF) and high sensitivity C-reactive protein (hs-CRP) in the model. RESULTS: DHA level, but not EPA level, was significantly associated with CES-D scores. Taking omega-3 supplements was associated with lower CES-D scores even when adjusting for CRF, while hs-CRP was non-significantly associated with CES-D scores. These findings suggest that DHA levels are related to depressive symptom severity. Omega-3 PUFA supplement use was associated with lower CES-D scores when controlling for EPA and DHA levels. CONCLUSION: The findings from this cross-sectional study suggest that lifestyle and/or other contextual factors unrelated to EPA and DHA levels may also be associated with depressive symptom severity. Longitudinal studies are needed to evaluate the role of health-related mediators among these relationships.

A randomized, double-blind, placebo-controlled trial of lamotrigine for prescription corticosteroid effects on the human hippocampus.

In animals, stress and corticosteroid excess are associated with decreases in memory performance and hippocampal volume that may be prevented with agents that decrease glutamate release. Humans also demonstrate changes in memory and hippocampus with corticosteroids. In this report the effects of glutamate-release inhibitor lamotrigine on hippocampal structure and memory were examined in people receiving medically needed prescription corticosteroid therapy. A total of 54 outpatient adults (n = 28 women) receiving chronic (≥ 6 months) oral corticosteroid therapy were randomized to lamotrigine or placebo for 48 weeks. Declarative memory was assessed using the Rey Auditory Verbal Learning Test (RAVLT); structural magnetic resonance imaging (MRI) as well as single-voxel proton MR spectroscopy (1HMRS) focused on hippocampus were obtained at baseline and week 48. Utilizing a mixed-model approach, structural and biochemical data were examined by separate ANOVAs, and memory was assessed with a multi-level longitudinal model. RAVLT total scores demonstrated significantly better declarative memory performance with lamotrigine than placebo (p = 0.047). Hippocampal subfield volumes were not significantly different between the treatment groups. In summary, lamotrigine was associated with less decline in declarative memory performance than placebo in corticosteroid-treated patients. Findings suggest that, in humans as well as in animal models, glutamate release inhibitors may attenuate some of the effects on the human memory associated with corticosteroids.

A Randomized, Double-Blind, Placebo-Controlled Trial of Escitalopram in Patients with Asthma and Major Depressive Disorder.

BACKGROUND: Depression is common in asthma and is associated with poor outcomes. However, antidepressant therapy in depressed patients with asthma has been the topic of little research. OBJECTIVE: This study examined the impact of antidepressant treatment with escitalopram versus placebo on the Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology-Self Report (IDS-SR), Asthma Control Questionnaire (ACQ), and oral corticosteroid use in patients with asthma and major depressive disorder (MDD). METHODS: Single-site 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of escitalopram (10 mg/d) was conducted in 139 outpatients with asthma and MDD. Randomization was stratified by oral corticosteroid use (≥3 bursts in past 12 months, yes or no) and baseline depressive symptom severity (HRSD score ≥ 20) (higher severity, n = 42) versus less than 3 bursts, HRSD score less than 20, or both (lower severity, n = 97). The primary data analysis was conducted using hierarchical linear modeling Version 7.01 on the higher and lower severity samples and post hoc was conducted on the combined sample. RESULTS: Among the higher severity completers (n = 21), a significant reduction in the ACQ score (P = .04) and oral corticosteroid use (P = .04) was observed with escitalopram. In the combined sample, no significant differences were observed, but a trend toward greater reduction in the IDS-SR score was observed with escitalopram (P = .07). Side effects were comparable across groups. CONCLUSIONS: The findings suggest that patients with more severe asthma and depression symptomatology may have a positive response, in terms of both asthma and depressive symptom reduction, to antidepressant treatment.

Neurosteroid Levels in Patients With Bipolar Disorder and a History of Cannabis Use Disorders.

PURPOSE/BACKGROUND: In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs). METHODS/PROCEDURES: Bipolar depressed participants were enrolled in a randomized placebo-controlled clinical trial to evaluate the efficacy of add-on pregnenolone for depression and before receiving pregnenolone or placebo. Baseline serum levels of neurosteroids (pregnenolone, allopregnanolone, pregnanolone, and androsterone) were analyzed in 53 participants with highly sensitive and specific gas chromatography/mass spectrometry. Current, active substance use disorders, or a positive baseline urine drug screen, were exclusionary. Participants were classified by past cannabis abuse or dependence diagnosis using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Data were analyzed by independent t tests for separate neurosteroids. FINDINGS/RESULTS: Participants with a history of CUD had higher serum pregnanolone, lower allopregnanolone, a higher pregnanolone to allopregnanolone ratio, and a lower pregnenolone to pregnanolone ratio compared with those without a history of cannabis use. Similar findings were not observed based on a history of other substance use disorders with the exception of lower allopregnanolone in those with opioid use disorders. Notably, the majority of those with an opioid use disorder also had a CUD (75%). IMPLICATIONS/CONCLUSIONS: These findings potentially suggest either enduring changes in neurosteroids in people with past CUDs or represent a vulnerability marker for a CUD.

A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine Dependence in Bipolar I Disorder.

OBJECTIVE: Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use. METHOD: A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale. RESULTS: In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed. CONCLUSIONS: Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit.

A randomized, double-blind, placebo-controlled trial of quetiapine in patients with bipolar disorder, mixed or depressed phase, and alcohol dependence.

BACKGROUND: Alcohol dependence is common in bipolar disorder (BPD) and associated with treatment nonadherence, violence, and hospitalization. Quetiapine is a standard treatment for BPD. We previously reported improvement in depressive symptoms, but not alcohol use, with quetiapine in BPD and alcohol dependence. However, mean alcohol use was low and a larger effect size on alcohol-related measures was observed in those with higher levels of alcohol consumption. In this study, efficacy of quetiapine in patients with BPD and alcohol dependence was examined in patients with higher mean baseline alcohol use than in the prior study. METHODS: Ninety outpatients with bipolar I or II disorders, depressed or mixed mood state, and current alcohol dependence were randomized to 12 weeks of sustained release quetiapine (to 600 mg/d) add-on therapy or placebo. Drinking was quantified using the Timeline Follow Back method. Additional assessment tools included the Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, Penn Alcohol Craving Scale, liver enzymes, and side effects. Alcohol use and mood were analyzed using a declining-effects random-regression model. RESULTS: Baseline and demographic characteristics in the 2 groups were similar. No significant between-group differences were observed on the primary outcome measure of drinks per day or other alcohol-related or mood measures (p > 0.05). Overall side effect burden, glucose, and cholesterol were similar in the 2 groups. However, a significant weight increase was observed with quetiapine at week 6 (+2.9 lbs [SE 1.4] quetiapine vs. -2.0 lbs [SE 1.4], p = 0.03), but not at week 12. Scores on the Barnes Akathisia Scale increased significantly more (p = 0.04) with quetiapine (+0.40 [SE 0.3]) than placebo (-0.52 [SE 0.3]) at week 6 but not week 12. Retention (survival) in the study was similar in the groups. CONCLUSIONS: Findings suggest that quetiapine does not reduce alcohol consumption in patients with BPD and alcohol dependence.

A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression.

Depression in bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n=80) with BPD, depressed mood state, were randomized to pregnenolone (titrated to 500 mg/day) or placebo, as add-on therapy, for 12 weeks. Outcome measures included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology-Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety (HRSA), and Young Mania Rating Scale (YMRS). Serum neurosteroid levels were assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA with a between factor of treatment assignment, a within factor (repeated) of visit, and the baseline value, as well as age and gender, as covariates. In participants with at least one postbaseline visit (n=73), a significant treatment by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was observed. Depression remission rates were greater in the pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (χ(2)(1)=3.99, p=0.046), but not the HRSD. Large baseline-to-exit changes in neurosteroid levels were observed in the pregnenolone group but not in the placebo group. In the pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in allopregnanolone (r(22)=-0.43, p=0.036) and pregNANolone (r(22)=-0.48, p=0.019) levels. Pregnenolone was well tolerated. The results suggest that pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered.

Does duloxetine improve cognitive function independently of its antidepressant effect in patients with major depressive disorder and subjective reports of cognitive dysfunction?

Introduction. Cognitive deficits are commonly reported by patients with major depressive disorder (MDD). Duloxetine, a dual serotonin/noradrenaline reuptake inhibitor, may improve cognitive deficits in MDD. It is unclear if cognitive improvements occur independently of antidepressant effects with standard antidepressant medications. Methods. Thirty participants with MDD who endorsed cognitive deficits at screening received 12-week duloxetine treatment. Twenty-one participants completed treatment and baseline and posttreatment cognitive testing. The Cambridge Neuropsychological Test Automated Battery was used to assess the following cognitive domains: attention, visual memory, executive function/set shifting and working memory, executive function/spatial planning, decision making and response control, and verbal learning and memory. Results. Completers showed significant cognitive improvements across several domains on tasks assessing psychomotor function and mental processing speed, with additional improvements in visual and verbal learning and memory, and affective decision making and response control. Overall significance tests for executive function tasks were also significant, although individual tasks were not, perhaps due to the small sample size. Most notably, cognitive improvements were observed independently of symptom reduction on all domains except verbal learning and memory. Conclusions. Patients reporting baseline cognitive deficits achieved cognitive improvements with duloxetine treatment, most of which were independent of symptomatic improvement. This trial is registered with NCT00933439.

A randomized, double-blind, placebo-controlled, trial of lamotrigine therapy in bipolar disorder, depressed or mixed phase and cocaine dependence.

Bipolar disorder is associated with very high rates of substance dependence. Cocaine use is particularly common. However, limited data are available on the treatment of this population. A 10-week, randomized, double-blind, placebo-controlled trial of lamotrigine was conducted in 120 outpatients with bipolar disorder, depressed or mixed mood state, and cocaine dependence. Other substance use was not exclusionary. Cocaine use was quantified weekly by urine drug screens and participant report using the timeline follow-back method. Mood was assessed with the Hamilton rating scale for depression, quick inventory of depressive symptomatology self-report, and young mania rating scale. Cocaine craving was assessed with the cocaine-craving questionnaire. Data were analyzed using a random regression analysis that used all available data from participants with at least one postbaseline assessment (n=112). Lamotrigine and placebo groups were similar demographically (age 45.1±7.3 vs 43.5±10.0 years, 41.8% vs 38.6% women). Urine drug screens (primary outcome measure) and mood symptoms were not significantly different between groups. However, dollars spent on cocaine showed a significant initial (baseline to week 1, p=0.01) and by-week (weeks 1-10, p=0.05) decrease in dollars spent on cocaine, favoring lamotrigine. Few positive trials of medications for cocaine use, other than stimulant replacement, have been reported, and none have been reported for bipolar disorder. Reduction in amount of cocaine use by self-report with lamotrigine suggests that a standard treatment for bipolar disorder may reduce cocaine use. A study limitation was weekly assessment of urine drug screens that decreased the ability to detect between-group differences.

Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison.

OBJECTIVE: Most patients with major depressive disorder (MDD) require second-step treatments to achieve remission. The Treatment with Exercise Augmentation for Depression (TREAD) study was designed to test the efficacy of aerobic exercise as an augmentation treatment for MDD patients who had not remitted with antidepressant treatment. METHOD: Eligible participants in this randomized controlled trial were sedentary individuals (men and women aged 18-70 years) diagnosed with DSM-IV nonpsychotic MDD who had not remitted with selective serotonin reuptake inhibitor (SSRI) treatment. Participants were recruited through physician referrals and advertisements. A total of 126 participants were randomized to augmentation treatment with either 16 kcal per kg per week (KKW) or 4 KKW of exercise expenditure for 12 weeks while SSRI treatment was held constant. Supervised sessions were conducted at The Cooper Institute, Dallas, Texas, with additional home-based sessions as needed to fulfill the weekly exercise prescription. The primary outcome was remission (as determined by a score ≤ 12 on the Inventory of Depressive Symptomatology, Clinician-Rated). The study took place between August 2003 and August 2007. RESULTS: There were significant improvements over time for both groups combined (F1,121 = 39.9, P < .0001), without differential group effect (group effect: F1,134 = 3.2, P = .07; group-by-time effect: F1,119 = 3.8, P = .06). Adjusted remission rates at week 12 were 28.3% versus 15.5% for the 16-KKW and 4-KKW groups, respectively, leading to a number needed to treat (NNT) of 7.8 for 16 KKW versus 4 KKW. Men, regardless of family history of mental illness, and women without a family history of mental illness had higher remission rates by week 12 with higher-dose (women, 39.0%; men, 85.4%) than with lower-dose exercise (women, 5.6%; men, 0.1%) (women: t95 = 2.1, P = .04; men: t88 = 5.4, P < .0001) (NNT: women, 3.0; men, 1.2). CONCLUSIONS: There was a trend for higher remission rates in the higher-dose exercise group (P < .06), with a clinically meaningful NNT of 7.8 in favor of the high exercise dose. Significant differences between groups were found when the moderating effects of gender and family history of mental illness were taken into account and suggest that higher-dose exercise may be better for all men and for women without a family history of mental illness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00076258.

Insomnia in patients with depression: a STAR*D report.

INTRODUCTION: Insomnia symptoms, which are common in depression, have a significant impact on function and quality of life. However, little is known about the prevalence and associated features of insomnia symptoms in representative treatment-seeking patients with depression. METHODS: Data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were analyzed. STAR*D recruited 3,743 adult outpatients diagnosed with nonpsychotic major depressive disorder (MDD) from primary (n=18) and psychiatric care (n=23) clinics across the United States. Baseline sociodemographic and clinical features were compared between those with insomnia symptoms (84.7%) and those without (15.3%). RESULTS: The most common presentation was the simultaneous presence of sleep onset, mid-nocturnal, and early morning insomnia symptoms (27.1%). Of these three types of insomnia symptoms, mid-nocturnal insomnia symptoms were the most commonly found alone (13.5%) and in combination with one or more other types (82.3%). Insomnia symptoms were associated with several indicators of a more severe depressive illness. Only a small proportion of participants with insomnia symptoms were receiving treatment for sleep disturbances at study initiation, and the vast majority of those receiving treatment still reported having insomnia symptoms. CONCLUSION: In outpatients who seek treatment for nonpsychotic MDD in typical clinical settings, insomnia symptoms are very common, undertreated, and indicative of a more severe depression.

A computerized decision support system for depression in primary care.

OBJECTIVE: In 2004, results from The Texas Medication Algorithm Project (TMAP) showed better clinical outcomes for patients whose physicians adhered to a paper-and-pencil algorithm compared to patients who received standard clinical treatment for major depressive disorder (MDD). However, implementation of and fidelity to the treatment algorithm among various providers was observed to be inadequate. A computerized decision support system (CDSS) for the implementation of the TMAP algorithm for depression has since been developed to improve fidelity and adherence to the algorithm. METHOD: This was a 2-group, parallel design, clinical trial (one patient group receiving MDD treatment from physicians using the CDSS and the other patient group receiving usual care) conducted at 2 separate primary care clinics in Texas from March 2005 through June 2006. Fifty-five patients with MDD (DSM-IV criteria) with no significant difference in disease characteristics were enrolled, 32 of whom were treated by physicians using CDSS and 23 were treated by physicians using usual care. The study's objective was to evaluate the feasibility and efficacy of implementing a CDSS to assist physicians acutely treating patients with MDD compared to usual care in primary care. Primary efficacy outcomes for depression symptom severity were based on the 17-item Hamilton Depression Rating Scale (HDRS(17)) evaluated by an independent rater. RESULTS: Patients treated by physicians employing CDSS had significantly greater symptom reduction, based on the HDRS(17), than patients treated with usual care (P < .001). CONCLUSIONS: The CDSS algorithm, utilizing measurement-based care, was superior to usual care for patients with MDD in primary care settings. Larger randomized controlled trials are needed to confirm these findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00551083.

Barriers to implementation of a computerized decision support system for depression: an observational report on lessons learned in "real world" clinical settings.

BACKGROUND: Despite wide promotion, clinical practice guidelines have had limited effect in changing physician behavior. Effective implementation strategies to date have included: multifaceted interventions involving audit and feedback, local consensus processes, marketing; reminder systems, either manual or computerized; and interactive educational meetings. In addition, there is now growing evidence that contextual factors affecting implementation must be addressed such as organizational support (leadership procedures and resources) for the change and strategies to implement and maintain new systems. METHODS: To examine the feasibility and effectiveness of implementation of a computerized decision support system for depression (CDSS-D) in routine public mental health care in Texas, fifteen study clinicians (thirteen physicians and two advanced nurse practitioners) participated across five sites, accruing over 300 outpatient visits on 168 patients. RESULTS: Issues regarding computer literacy and hardware/software requirements were identified as initial barriers. Clinicians also reported concerns about negative impact on workflow and the potential need for duplication during the transition from paper to electronic systems of medical record keeping. CONCLUSION: The following narrative report based on observations obtained during the initial testing and use of a CDSS-D in clinical settings further emphasizes the importance of taking into account organizational factors when planning implementation of evidence-based guidelines or decision support within a system.

The effect of pain on outcomes in a trial of duloxetine treatment of major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) frequently report one or more pain symptoms. To explore the relationship between improvement in pain symptoms and MDD treatment outcomes, we conducted a secondary analysis of an approximately 12-week, open label trial of duloxetine in MDD. The primary objective was to test the hypothesis that a greater reduction in pain was associated with a higher probability of MDD remission. METHODS: Adults with DSM-IV MDD were enrolled in the study if they had a Hamilton Depression Scale (HAMD-17) total score of 15 or more and a Clinical Global Impression of Severity (CGI-S) score of 4 or more. The duloxetine dose of patients could be titrated on the basis of the degree of response within the range from 60 to 120 mg given QD, with 90 mg QD as an intermediate dose. Remission of major depressive disorder was defined as a HAMD-17 total score of < or = 7. Core emotional symptoms of depression were determined by the HAMD-17 Maier subscale. Pain was assessed using a 100 mm visual analog scale (VAS) of overall pain severity over the last week (0 = no pain, 100 = pain as severe as I can imagine). For the primary analysis, mean change in VAS overall pain score over time was compared between remitters and non-remitters at endpoint using a mixed model repeated measures approach. RESULTS: Two hundred forty nine patients were included in the analysis. A greater reduction in pain was associated with a significantly higher probability of remission of MDD, after accounting for changes in the core emotional symptoms. Greater pain reduction was associated with significant improvement in MDD core emotional symptoms. A greater improvement in pain was also associated with improvements in patient and clinician-rated global assessments. CONCLUSIONS: The effective treatment of pain symptoms in patients with major depressive disorder was associated with higher remission rates. The results underscore the importance of effectively treating painful symptoms associated with depression.

TREAD: TReatment with Exercise Augmentation for Depression: study rationale and design.

BACKGROUND: Despite recent advancements in the pharmacological treatment of major depressive disorder (MDD), over half of patients who receive treatment with antidepressant medication do not achieve full remission of symptoms. There is evidence that exercise can reduce depressive symptomatology when used as a treatment for MDD. However, no randomized controlled trials have evaluated exercise as an augmentation strategy for patients with carefully diagnosed MDD who remain symptomatic following an adequate acute phase trial of antidepressant therapy. PURPOSE: TReatment with Exercise Augmentation for Depression (TREAD) is an NIMH-funded, randomized, controlled trial designed to assess the relative efficacy of two doses of aerobic exercise to augment selective serotonin reuptake inhibitor (SSRI) treatment of MDD. METHODS: The TREAD study includes 12 weeks of acute phase treatment with a 12-week post-treatment follow-up. In addition to looking at change in depressive symptoms as a primary outcome, it also includes comprehensive assessment of psychosocial function and treatment adherence. RESULTS: This paper reviews the rationale and design of TREAD and illustrates how we address several key issues in contemporary patient-oriented research on MDD: 1) the use of augmentation strategies in the treatment of depressive disorders in general, 2) the use of non-pharmacological strategies in the treatment of depressive disorders, 3) the considerations of designing a well-controlled trial using two active treatment groups, and 4) the implementation of an adherence program for the use of exercise as a treatment strategy. CONCLUSIONS: The TREAD study is uniquely designed to overcome sources of potential bias and threats to internal and external validity that have limited prior research on the mental health effects of exercise. The study is facilitated by the development of a multidisciplinary research team that includes experts in both depression treatment and exercise physiology, as well as other related fields.

A computerized clinical decision support system as a means of implementing depression guidelines.

The authors describe the history and current use of computerized systems for implementing treatment guidelines in general medicine as well as the development, testing, and early use of a computerized decision support system for depression treatment among "real-world" clinical settings in Texas. In 1999 health care experts from Europe and the United States met to confront the well-documented challenges of implementing treatment guidelines and to identify strategies for improvement. They suggested the integration of guidelines into computer systems that is incorporated into clinical workflow. Several studies have demonstrated improvements in physicians' adherence to guidelines when such guidelines are provided in a computerized format. Although computerized decision support systems are being used in many areas of medicine and have demonstrated improved patient outcomes, their use in psychiatric illness is limited. The authors designed and developed a computerized decision support system for the treatment of major depressive disorder by using evidence-based guidelines, transferring the knowledge gained from the Texas Medication Algorithm Project (TMAP). This computerized decision support system (CompTMAP) provides support in diagnosis, treatment, follow-up, and preventive care and can be incorporated into the clinical setting. CompTMAP has gone through extensive testing to ensure accuracy and reliability. Physician surveys have indicated a positive response to CompTMAP, although the sample was insufficient for statistical testing. CompTMAP is part of a new era of comprehensive computerized decision support systems that take advantage of advances in automation and provide more complete clinical support to physicians in clinical practice.