Antidepressant Medication Treatment Research Articles

Maximizing the Adequacy of Medication Treatment in Controlled Trials and Clinical Practice: STAR*D Measurement-Based Care

The success of well-developed protocols has been limited in real-world practice, where even effective strategies have not been sufficient to meet patient needs in routine clinical care owing to Axis I and III comorbidities. The Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) trial required that antidepressant medication treatment be optimal regarding dose and duration, yet accommodate flexibility to ensure safety given the wide range of comorbid general medical and psychiatric disorders allowed in the trial. The objective of this study was to develop a measurement-based care (MBC) approach and an automated feedback system to ensure adequate and safe antidepressant treatment delivery suitable for both clinical research and routine practice. Ratings of depressive symptom severity and side-effect frequency, intensity, and burden were obtained at each treatment visit using the MBC system that (1) guided medication dose adjustments and treatment duration, (2) documented clinician adherence to treatment recommendations, and (3) provided prompt feedback to clinicians to enhance appropriate treatment decisions. Physician adherence to protocol-specific treatment was monitored based on measured symptoms and side-effect burden, and dose and duration of antidepressant at each critical decision point during the acute phase treatment of major depression. Feedback was provided at the point of care by the clinical coordinators, assisted by Web-based reports following each treatment visit. On the basis of the first treatment step with citalopram, over 85% of treatment encounters had appropriate fidelity to recommendations. Most deviations from treatment recommendations occurred late in treatment and were often justifiable. MBC proved to be feasible and effective in busy primary and psychiatric settings. This approach signals a paradigm shift toward the use of measurement-based clinical decisions, both at the point of care and following each visit, to deliver optimal pharmacotherapy for depression.

The Prevalence and Use of Antidepressant Medication in Pediatric Cancer Patients

During the period of cancer diagnosis and active treatment, several small case series have revealed high rates of psychiatric difficulty in pediatric patients. However, due to the methodological limitations in these studies, it remains impossible to determine accurately the true prevalence of mood disorders in pediatric cancer patients receiving cancer treatment. To date, no study has reported rates of antidepressant treatment in this population. The aims of this study were: (1) To determine the prevalence of the use of antidepressant medication (ADM) in children with cancer; (2) to identify a group of children being treated for cancer, that are likely to receive ADM, and who therefore may be eligible for a prospective observational or interventional clinical trial of depression during cancer therapy. We reviewed the medical records of 224 pediatric patients suspected for cancer in 2003 at the Children's Medical Center of Dallas. Of these, 6 proved non-oncologic and 2 were lost to follow up, leaving 216 charts for review. Within 1 year of diagnosis, 29 patients (13%) had received a psychiatric consultation. Twenty-two patients (10.2%) received ADM within 1 year of cancer diagnosis. Children >/= 12 years, children with acute lymphoblastic leukemia, and children receiving radiotherapy or opiate analgesics were more likely to receive ADM by multivariate analysis. Race, sex, bone marrow transplant, and surgery were not significantly associated with ADM use. The prevalence of ADM use in pediatric cancer patients (10.2%) was higher than the reported rates of depression (4-8%) and ADM treatment (1%) in the general pediatric population. Teenagers and those who received opiate analgesic medications during their cancer therapy represent a subgroup of children in whom further study of depression and cancer therapy may be valuable.

Psychosocial Functioning of Medicaid Recipients With Major Depression

Back to table of contents Previous article Next article LettersFull AccessLettersSteven C. Marcus Ph.D.Mark Olfson M.D., M.P.H.Steven C. Marcus Ph.D.Search for more papers by this authorMark Olfson M.D., M.P.H.Search for more papers by this authorPublished Online:1 Jul 2006https://doi.org/10.1176/ps.2006.57.7.1046AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Psychosocial Functioning of Medicaid Recipients With Major DepressionTo the Editor: Confounding of treatment selection by illness severity threatens many nonexperimental observational research designs that use administrative data to study mood disorders ( 1 , 2 ). In a study of antidepressants and suicide, for example, if depressed patients who receive antidepressants are more severely ill than ostensibly similar depressed patients who do not receive antidepressants, an observed association between antidepressant treatment and suicide may simply reflect this underlying selection bias. Because measures of illness severity are not routinely available in administrative data sets, it is unclear whether or to what extent this bias exists. We sought to evaluate whether psychosocial functioning differs among patients with major depressive disorder on the basis of their use of antidepressant medications or psychotherapy. We merged a 1993-1994 Medicaid claims database containing patient diagnostic and service use data with a community-tracking database that includes a clinician-administered Global Assessment of Functioning (GAF) ( 3 ) rating. During this period, there was a low level of managed care penetration and a high level of data completeness. Patients selected had received a diagnosis of major depressive disorder ( ICD-9 codes 296.2 or 296.3) that was preceded by a period of at least 60 days without antidepressant treatment and had also received a GAF rating within 60 days preceding the first noted diagnosis of major depressive disorder. Filled prescriptions for antidepressant medications were noted in the 60 days after the diagnosis of major depression. A similar algorithm was used to examine GAF ratings and use of psychotherapy. A total of 472 patients were identified for the antidepressant analysis; 159 (34 percent) had filled a prescription for an antidepressant in the 60 days after the diagnosis of major depressive disorder. The mean±SD GAF score of the group that initiated antidepressant medications (49.6±13.1) did not significantly differ from that of the group that did not initiate antidepressants (50.1±11.7). The GAF score of the 341 patients who received psychotherapy (50.3±12.2) was similar to that of the 175 patients who did not receive psychotherapy (49.7±12.0). The findings stratified by age (six to 20 years and 21 years and older) directly mirrored the overall findings for both antidepressant and psychotherapy use.Under these conditions, neither initiation of antidepressant medication nor psychotherapy treatment was significantly related to illness severity as measured by a clinician-administered GAF. The study's limitations include relatively small samples, a concern that clinician-administered GAF ratings are only weakly related to function and outcome ( 4 ), an absence of documented standardization of the GAF ratings, and temporal delays between the GAF ratings and treatment. Within the context of these limitations, the similarities in mean GAF ratings for these groups may help to reduce concern over confounding of treatment initiation and illness severity. Dr. Marcus is affiliated with the School of Social Policy and Practice, University of Pennsylvania, Philadelphia. Dr. Olfson is with the Department of Psychiatry, College of Physicians and Surgeons of Columbia University and the New York State Psychiatric Institute, New York.

Cognitive Predictors of Response to Treatment for Depression in Multiple Sclerosis

Cognitive impairment, particularly in the domain of executive functioning, has been demonstrated to predict poorer antidepressant medication treatment response. In this investigation, neuropsychological functioning was evaluated as a predictor of depression treatment response among 59 patients with multiple sclerosis. Performance on a Stroop task accounted for 28.7% of the variance in poorer pharmacologic antidepressant treatment response, as compared to less than 1% of the variance in two psychotherapy conditions. These results provide preliminary evidence to suggest that performance on neuropsychological measures may predict antidepressant treatment response in multiple sclerosis.

Guideline Watch: Practice Guideline for the Treatment of Patients With Major Depressive Disorder, 2nd Edition

Since the publication in 2000 of APA’s Practice Guideline for the Treatment of Patients With Major Depressive Disorder (2nd Edition) (1), two important safety concerns have emerged (hepatotoxicity with nefazodone, and suicide risk and antidepressants), and two new antidepressants have been approved for use (escitalopram and duloxetine). This watch describes these developments as well as evidence that has accrued since 2000 in other areas related to the treatment of major depressive disorder.

Fluoxetine in adolescents with comorbid major depression and an alcohol use disorder: a 3-year follow-up study

The goal of this 3-year follow-up evaluation was to determine whether the decreases in drinking and in depressive symptoms that were noted during our acute phase study with fluoxetine in comorbid adolescents persisted at a 3-year follow-up evaluation. At the 3-year follow-up evaluation, the group continued to demonstrate significantly fewer DSM criteria for an AUD and fewer BDI depressive symptoms and also consumed fewer standard drinks than they had demonstrated at the baseline of the acute phase study. However, 7 of the 10 participants demonstrated MDD at the 3-year follow-up assessment, and 4 demonstrated an AUD. The presence of a MDD was significantly correlated with the presence of an AUD at both the 1-year and the 3-year follow-up assessments. Four of the participants restarted SSRI medications during the follow-up period. Half of the subjects graduated from college during the 3-year assessment period, despite their residual depressive symptoms and drinking. We conclude that the long-term therapeutic effects of an acute phase trial of fluoxetine plus psychotherapy slowly decrease but did not disappear when fluoxetine is discontinued shortly after the acute phase trial. The high rate of MDD at follow-up suggests that longer term antidepressant medication treatment may be needed for at least some comorbid adolescents.

One size fits some: the impact of patient treatment attitudes on the cost-effectiveness of a depression primary-care intervention

Despite their impact on outcomes, the effect of patient treatment attitudes on the cost-effectiveness of health-care interventions is not widely studied. This study estimated the impact of patient receptivity to antidepressant medication on the cost-effectiveness of an evidence-based primary-care depression intervention. Twelve community primary-care practices were stratified and then randomized to enhanced (intervention) or usual care. Subjects included 211 patients beginning a new treatment episode for major depression. At baseline, 111 (52.6%) and 145 (68.7%) reported receptivity to antidepressant medication and counseling respectively. The intervention trained the primary-care teams to assess, educate, and monitor depressed patients. Twelve-month incremental (enhanced minus usual care) total costs and quality-adjusted life years (QALYs) were calculated. Among patients receptive to antidepressants, the mean incremental cost-effectiveness ratio was dollar 5,864 per QALY (sensitivity analyses up to dollar 14,689 per QALY). For patients not receptive to antidepressants, the mean incremental QALY score was negative (for both main and sensitivity analyses), or the intervention was at least no more effective than usual care. These findings suggest a re-thinking of the 'one size fits all' depression intervention, given that half of depressed primary-care patients may be non-receptive to antidepressant medication treatment. A brief assessment of treatment receptivity should occur early in the treatment process to identify patients most likely to benefit from primary-care quality improvement efforts for depression treatment. Patient treatment preferences are also important for the development, design, and analysis of depression interventions.

Relationship Between Antidepressant Medication Treatment and Suicide in Adolescents

Relationship Between Antidepressant Medication Treatment and Suicide in Adolescents

The impact of treatment-resistant depression on health care utilization and costs.

Approximately 50% of patients diagnosed with major depressive disorder will experience a recurrent or chronic course of illness for which long-term treatment is recommended. Moreover, at least 20% of patients diagnosed with depression do not respond satisfactorily to several traditional antidepressant medication treatment trials. Very little is known about the health care costs of patients with treatment-resistant depression. Based on medical claims data (MarketScan Research Database, The MEDSTAT Group, Cambridge, Mass.) from January 1, 1995, to June 30, 2000, a naturalistic, retrospective analysis was conducted to study the characteristics and health care utilization of patients with treatment-resistant depression. All patients having an International Classification of Diseases, Ninth Revision (ICD-9), diagnosis code for unipolar or bipolar depression with specified antidepressant dosing and treatment durations were initially selected. Patients were then classified as "treatment resistant" if either they switched from or augmented initial antidepressant medication with other antidepressants at least twice (outpatient treatment-resistant group) or they switched from or augmented their initial antidepressant medication and also had a claim for either a depression-related hospitalization or suicide attempt (hospitalized treatment-resistant group). Those meeting the initial medication and diagnosis selection criteria but not meeting the treatment-resistance criteria constituted the comparison group. Members of the comparison group had comparatively stable antidepressant medication use patterns, consistent with an acceptable response to treatment. Patients were followed for a minimum of 9 months. Resource utilization was calculated from index date to last available claims data point and then annualized. Treatment-resistant patients were more likely to be diagnosed with bipolar disorder or concurrent substance abuse or anxiety disorders than the comparison group (p <.001). Treatment-resistant patients were at least twice as likely to be hospitalized (general medical and depression related) and had at least 12% more outpatient visits (p <.02). Treatment resistance was also associated with use of 1.4 to 3 times more psychotropic medications (including antidepressants) (p <.001). Patients in the hospitalized treatment-resistant group had over 6 times the mean total medical costs of non-treatment-resistant depressed patients ($42,344 vs. $6512) (p <.001) and their total depression-related costs were 19 times greater than those of patients in the comparison group ($28,001 vs. $1455) (p <.001). Treatment-resistant depression is costly and associated with extensive use of depression-related and general medical services. These findings underscore the need for early identification and effective long-term maintenance treatment for treatment-resistant depression.

Sexual Function and Satisfaction in the Treatment of Chronic Major Depression With Nefazodone, Psychotherapy, and Their Combination

Changes in sexual interest/satisfaction and function are frequently associated with major depression and the use of some antidepressant treatments. This study compares the effects of antidepressant medication, psychotherapy, and combined treatment on sexual interest/satisfaction and function in patients with chronic major depression. Outpatients with chronic forms of DSM-IV major depressive disorder (N = 681) were randomly assigned to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. The Modified Rush Sexual Inventory was used to assess sexual functioning, and the 24-item Hamilton Rating Scale for Depression was used to assess depressive symptoms. At baseline, 65% of men and 48% of women reported some sexual dysfunction. Statistically significant linear improvement in sexual interest/satisfaction was noted across all 3 treatment groups (p < .001). Additionally, significant improvement in sexual function was observed across all 3 treatment groups on a composite measure of female sexual function (p < .001). Controlling for depressive symptoms and gender, combined treatment produced greater improvement in total sexual interest/satisfaction than CBASP alone (p = .007), but was not significantly different from nefazodone alone. Improvement in depressive symptoms was associated with improved sexual interest/satisfaction for men and women and, for men, improved sexual functioning. Chronic depression is associated with high rates of sexual dysfunction. Treatment with nefazodone, CBASP, and combined treatment improved sexual interest/satisfaction, with greatest improvement observed with combined treatment.

National Patterns of Medication Treatment for Depression, 1987 to 2001.

BACKGROUND: We investigated trends in antidepressant use, as well as broader changes in depression treatment, following the availability of selective serotonin reuptake inhibitors (SSRIs). METHOD: Using data from the National Disease and Therapeutic Index, a nationally representative survey of U.S. office-based physicians conducted by IMS HEALTH, we analyzed trends in antidepressant prescribing patterns from 1987 through the third quarter of 2001. Annual sample sizes of physician visits by patients reported to have depression ranged from 3901 visits in 1987 to 6639 in 1998. Outcomes examined included the frequency of depression visits, the likelihood of antidepressant therapy, and the use of specific medications. RESULTS: The estimated national number of physician visits by patients with depression increased from 14.4 million visits in 1987 to 24.5 million in 2001 (annualized). The rate of antidepressant medication treatment in these patients also increased from 70% in 1987 to 89% in 2001. In 1987, tricyclic antidepressants were prescribed to 47% of patients with depression. The most common individual antidepressants were amitriptyline (14%), trazodone (12%), doxepin (8%), and desipramine (6%). In 1989, a year after its introduction, fluoxetine was prescribed to 21% of patients with depression. The introduction of other SSRIs led aggregate SSRI use to grow to 38% in 1992, 60% in 1996, and 69% in 2000. In 2001, sertraline (18%), paroxetine (16%), fluoxetine (14%), citalopram (13%), and bupropion (9%) were the leading antidepressants, while tricyclics were used in only 2% of patients. The use of benzodiazepines in depression declined from 21% of patients in 1987 to 8% in 2001. CONCLUSION: The increasing therapeutic dominance of SSRIs may have contributed to other changes in depression treatment, including declining benzodiazepine use, increased aggregate antidepressant treatment rates, and increased reporting of depression.

Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care

Objectives: To determine whether problem solving treatment combined with antidepressant medication is more effective than either treatment alone in the management of major depression in primary care. To assess the...

The effect of treatment on the two-year course of late-life depression.

The purpose of this study was to examine the effect of treatment on the long-term course of geriatric depression. Eighty-four elderly patients who had responded to treatment of the index episode of major depression were maintained on full-dose antidepressant medication and followed on a monthly basis for two years. Relapse and recurrence were treated in a systematic manner. The cumulative probability of surviving for two years without relapse or recurrence was 74%. Of the 14 patients who suffered recurrence following recovery from the index episode, all responded to a change of treatment, and 71% remained well for the remainder of the study. The risk of recurrence was significantly increased by a delayed response to treatment of the index episode. Continuation and maintenance treatment with full-dose antidepressant medication, frequent follow-up, and vigorous treatment of relapses and recurrences, were associated with a good outcome in this group of elderly patients.

Effect of pharmacotherapy on suicidal ideation and behavior

AbstractSuicide has become an important public health issue. It is the eighth leading cause of death among adults and varies between the second and third leading cause of death for youth under the age of 24 years. Suicidal ideation is a common symptom of psychiatric disorders; over 55% of individuals with mental disorders report suicidal ideation at some point in their lives. Fully 25% of individuals with mental disorders make at least one lifetime suicide attempt and over 12% make multiple suicide attempts. Suicidal ideation and suicidal acts are most prevalent in individuals with mood disorders. Almost 17% of individuals with either major depression or dysthymia make at least one suicide attempt while over 28% of individuals with bipolar disorders attempt suicide. Intensification of suicidal thoughts and behavior can occur in depressed patients undergoing active treatment, including antidepressant pharmacotherapy, and the risk may persist until remission occurs. Within this context, it is likely that reports linking the SSRI fluoxetine (and other antidepressants) with intensification of suicidal ideation represent random occurrences rather than causation. Although it is possible that some type of aberration in CNS serotonergic function in rare individuals might be associated with an idiosyncratic response to serotonin‐specific medications, the retrospective meta‐analyses of a number of databases indicate there is no causal relationship between SSRI or other antidepressant medication treatment and the emergence of suicidal ideation or behavior. Rather, the available data support the conclusion that antidepressant pharmacotherapy diminishes suicidal ideation and acts. Depression 2:169–172 (1994/1995). © 1995 Wiley‐Liss, Inc.

Antidepressants and HIV infection: Effect of lithium chloride and desipramine on HIV replication

AbstractThere is increasing evidence that depression occurs in a significant number of individuals with HIV infection. Consequently, antidepressant medication treatment is often prescribed in an attempt to alleviate depressive symptoms and improve the quality of life. However, psychopharmacologic agents have direct effects on the immune system. Therefore we studied the effects of lithium chloride and the tricyclic antidepressant, desipramine, on HIV replication in T lymphocytes in culture. The effect of lithium on reverse transcriptase activity was also studied in vitro. Neither lithium nor desipramine had an effect on HW replication, and lithium had no effect on virus‐associated reverse transcriptase activity. Although these results suggest that lithium and desipramine can be used without adverse effects on HIV replication for the treatment of depression in HIV‐infected individuals, in vivo effects can not be ruled out by these in vitro findings. Depression 1:205‐209 (1993). © 1993 Wiley‐Liss, Inc.

Treatment of depression in cancer patients is associated with better life adaptation: a pilot study.

Major depression occurs in a significant number of cancer patients, and there is evidence that cancer patients with depression do not receive adequate antidepressant treatment. In an uncontrolled pilot study, the authors assess the degree of depression and the quality of life after the initiation of antidepressant medication treatment in 12 depressed cancer patients who received adequate antidepressant drugs and in 10 depressed cancer patients who received inadequate antidepressant treatment. These preliminary findings suggest that cancer patients with major depression benefit from antidepressant medication treatment and may experience an improved psychosocial adjustment to cancer. Controlled clinical trials will be necessary to verify these preliminary findings.

Sex Steroid Hormone Dynamics in Endogenous Depression: A Review

Depressive illnesses are a heterogeneous group of disorders that have dissimilar features in clinical symptoms, response to treatment, and, undoubtedly, etiology. Although anyone may suffer a depression, often precipitated by some identifiable major life stress, there is a type of depression that is characterized by a certain cluster of symptoms, a prolonged course, usually a family history of similar illness, and generally a responsiveness to only somatic therapies (antidepressant medication or electroconvulsive treatment [ЕСТ]). This type of depression, called endogenous (Kendell, 1976) or endogenomorphic (Klein, 1974) depression, also may follow an identifiable precipitating stress and thus be reactiveM in one sense. The particular symptom cluster and the requirement for somatic therapy are, however, the factors that primarily characterize such a depression as endogenous. The symptoms of endogenous or endogenomorphic depression have been codified in the Research Diagnostic Criteria (Spitzer, Endicott, & Robins, 1978) and in the American Psychiatric Association's (1980) Diagnostic and statistical manual of mental disorders (3rd ed.) DSM-III. They include, among others, anhedonia (inability to experience pleasure), lack of energy, fatigability, reduced sexual drive, anorexia, weight loss, sleep disturbance (especially early morning awakening), depression worse in the morning, self-