Depression and suicidal ideation in college students.

BACKGROUND/AIMS: Suicide is one of the leading causes of death in college students and is often associated with depression. The aim of this study was to assess the rates of suicidal ideation (SI) on college campuses and to identify its correlates. METHODS: On-campus depression screening sessions were conducted at 3 universities (n = 898; 55% female; mean age 20.07 ± 1.85 years). Participants completed the Beck Depression Inventory (BDI; mean ± SD of total score = 6.27 ± 6.31) and other measures. Eighty-four students endorsed a '1' on the BDI suicidality item, suggesting thoughts of suicide. RESULTS: Results showed that students with greater depression severity, higher levels of hopelessness, and poorer quality of life were more likely to endorse SI. CONCLUSION: Factors associated with SI highlighted in this study may aid in the identification of college students at risk for suicide.

The prevalence of compulsive eating and exercise among college students: an exploratory study.

Eating disturbances continue to grow among college students, and researchers have begun to investigate factors that may lead to abnormal eating behaviors in this population. Recent research has also suggested that excessive exercise can become a compulsive behavior that may affect psychological health. The aim of this exploratory study was to evaluate the relationships between both compulsive eating and exercise, and demographic and clinical variables in a college population. Participants were 589 undergraduates (mean age 20 years) recruited during a mental health screening at two different campuses. Participants completed a screening package of measures including a questionnaire about socio-demographic data, the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), the Consumptive Habits Questionnaire (CHQ), the Modified Overt Aggression Scale-Self-rated version (MOAS), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short version (QLESQ). A prevalence rate of 7.2% was found for compulsive eating and 18.1% for compulsive exercise, as measured by the CHQ. Only 11 participants (1.9%) reported both compulsive eating and exercise. There was no significant relationship between compulsive eating and compulsive exercise. The results suggest that college students may represent a group at high risk of developing abnormal eating behaviors and compulsive exercise.

Reach of benchmark psychiatric trial results to community-based providers: a case study of CATIE.

OBJECTIVE: To evaluate the familiarity of front-line clinicians with findings from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), the influence of didactic continuing medical education on provider knowledge about key details of CATIE, and how location-related factors affect rates of pre-event knowledge and intraevent learning about CATIE. METHOD: Data derived from the Massachusetts General Hospital Psychiatry Academy (MGH-PA) semester II live symposia provided in different cities nationally between September and December 2006 were analyzed to evaluate providers' self-assessment of their knowledge about CATIE. In addition, participants were also asked a preactivity and postactivity question to assess learning of material presented during the live event psychosis lecture. Descriptive statistics were utilized to characterize participants' self-assessment of knowledge about CATIE, while parametric and nonparametric statistical tests were used to evaluate the degree of observed learning and the effect of lecture location on the results. RESULTS: 3333 participants (mean attendance: N = 278 per event) attended 1 of the 12 MGH-PA live symposia. Of the subsample of providers who treat schizophrenia, 51% indicated that either they had never heard of CATIE or they were not familiar enough with its results to change their practice. Overall, the proportion of correct answers on the postactivity question was 65%, compared with 24% prior to the lecture (chi(2) = 48.68, df = 1, p < .001). Degree of learning did not differ among symposium locations. CONCLUSION: In this sample, the CATIE study had very limited dissemination to, and impact on, a geographically and occupationally diverse sample of mental health practitioners. Robust learning of a key methodologic detail of this trial was evidenced across symposium locations.

Enhancing the efficacy of antidepressants with psychotherapy.

Even after optimal treatment with and response to antidepressant medications during acute treatment of major depressive disorder, residual symptoms are common. Patients with residual symptoms are at increased risk of relapse and recurrence. Research suggests that psychotherapy may play an important role in enhancing the effects of antidepressant drug therapy and improving patients' long-term prognosis. Psychotherapy targets specific symptoms associated with relapse (e.g., guilt, hopelessness, negativity, low self-esteem) that antidepressants may not, reduces residual symptoms (e.g., irritability), improves coping skills for long-term disease management and promotes sustained, healthy cognitive changes. In addition, neuroimaging data suggest that psychotherapy and pharmacotherapy target different primary sites of the cortical-limbic pathway with differential top-down and bottom-up effects, resulting in modulation of critical common targets and facilitation of disease remission. The use of adjunctive psychotherapy in the acute phase of depression treatment appears to provide only a modest increase in response rates, although combined pharmaco-psychotherapy may prevent or delay relapse. Simultaneous application of pharmacotherapy and psychotherapy during the maintenance phase does not consistently provide a clear advantage over maintenance pharmacotherapy. In contrast, sequential use of psychotherapy after induction of remission with acute antidepressant drug therapy may confer a better long-term prognosis in terms of preventing relapse or recurrence and, for some patients, may be a viable alternative to maintenance medication therapy.

A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder.

CONTEXT: Pattern analysis suggests that "true" drug response is characterized by clinical improvement that is not subsequently followed by a worsening of symptoms (sustained clinical response). To date, several reports demonstrate that early response rates are equivalent between antidepressant-treated and placebo-treated groups of patients with major depressive disorder, suggesting that patients who demonstrate significant and sustained symptom improvement during the first 2 weeks of treatment are not responding to the antidepressant itself, but to nonspecific, placebo-like factors. OBJECTIVE: To compare early sustained response rates between antidepressant- and placebo-treated adults with major depressive disorder. DATA SOURCES: Medline/Pubmed were searched. No year of publication limits were used. STUDY SELECTION: Randomized, double-blind, placebo-controlled antidepressant trials or pooled reports/meta-analyses of such trials reporting early sustained response rates for major depressive disorder. The decision to include studies in the meta-analysis was performed by 2 reviewers. DATA EXTRACTION: Data were extracted with the use of a precoded form. DATA SYNTHESIS: Analyses were performed on the proportion of patients who achieved a sustained response the first 2 weeks of treatment, as well as the first week of treatment. A random-effects model with fixed drug effects was used to combine the studies and make comparisons of sustained early response rates between antidepressant- and placebo-treated groups. Data from 8 reports involving a total of 7121 major depressive disorder patients (4076 randomized to treatment with an antidepressant and 3045 randomized to placebo) were analyzed. Antidepressant-treated patients were more likely to demonstrate sustained clinical response by 2 weeks (odds ratio 2.06, 95% CI: 1.52-2.8) or 1 week of treatment (odds ratio 1.50, 95% CI: 1.08-2.08) than placebo-treated patients. CONCLUSIONS: The results of the present analysis suggest that "true" drug response can occur the first 2 week as well as the first week of treatment of major depressive disorder with conventional antidepressants.

Adjunctive atomoxetine for residual fatigue in major depressive disorder.

OBJECTIVE: To assess the effectiveness and safety of atomoxetine as an adjunctive medication for residual fatigue in a naturalistic treatment setting. METHODS: A retrospective chart review was conducted to identify major depressive disorder (MDD) patients who had experienced significant symptom improvement (either partial response or remission) following treatment with conventional antidepressants but who were continuing to complain of fatigue. Fourteen such patients (42.2+/-13.4 years of age, five women, baseline HDRS 6.2+/-2.4) with a 17-item Hamilton Depression Rating Scale (HDRS17)<11 who received adjunctive atomoxetine for fatigue were included in the report. Antidepressants augmented were the selective serotonin reuptake inhibitors (SSRIs) (n=11; 78.6%), mirtazapine (n=2, 14.3%), and amitriptyline (n=1, 7.1%). RESULTS: Twelve (85.7%) patients (nine remitters, three partial responders) received at least 4 weeks of atomoxetine treatment. The remaining two (partial responders) discontinued atomoxetine within 1-3 days due to increased anxiety. The brief fatigue inventory (BFI) and Clinical Global Impressions Scale (CGI) were administered when atomoxetine was first prescribed, and following 4-10 weeks of treatment (mean of 5.4+/-1.8 weeks). There was a significant decrease in BFI scores (41.9+/-14.9 versus 24.3+/-13.4, p=0.0015), and HDRS-17 scores (6.2+/-2.4 versus 3.5+/-2.8, p=0.0466), but not CGI-S scores (1.3+/-1.4-1.0+/-0.0, p=0.08) following treatment with atomoxetine. 5/12 (41.6%) patients had a 50% or greater decrease in BFI scores. All 12 patients were remitters at follow-up. The mean atomoxetine dose was 42.8+/-10.6 mg. Side effects included insomnia (n=6), increased anxiety (n=3), nausea (n=1) and dry mouth (n=1). CONCLUSIONS: Although preliminary, these results suggest a possible augmentation role for atomoxetine when used in conjunction with conventional antidepressants for residual fatigue in MDD. Prospective as well as controlled studies are necessary to further explore the role of atomoxetine augmentation in MDD.

Presenting characteristics of depressed outpatients as a function of recurrence: preliminary findings from the STAR*D clinical trial.

OBJECTIVES: Recurrent depression predicts risk for subsequent episodes, but it is unclear how it relates to demographic features, course of illness, and clinical presentation. METHODS: We report on the baseline data for the first 1500 patients enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org). Patients were required to have a DSM-IV diagnosis of nonpsychotic major depression and to score > or = 14 on the 17-item Hamilton rating scale for depression. Status with respect to recurrent depression and other aspects of illness course and demographic features were ascertained at intake, along with measures of depression and concurrent general medical illness. RESULTS: Patients with recurrent depression were older, had an earlier age of onset, and were more likely to have a positive family history of depression than first episode patients. However, recurrent patients were less likely to be chronic and reported shorter current episodes than first episode patients, something that was largely confined to females. Recurrent patients were more likely than first episode patients to report non-essential aspects of mood, cognition, and somatic symptoms, although largely as a consequence of greater overall depressive symptom severity. CONCLUSIONS: As compared to single episode depressions, recurrent depression was associated with greater symptom severity and illness characteristics suggestive of greater underlying risk, but not other demographic characteristics than age. Risk for recurrence appeared to be distinct from chronic depression. A subset of chronic first episode patients may lack the capacity to remit and may therefore be distinct from those with recurrent episodes.

Aripiprazole augmentation of selective serotonin reuptake inhibitors for treatment-resistant major depressive disorder.

BACKGROUND: Due to their favorable side effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Aripiprazole, an atypical antipsychotic agent with partial dopaminergic and serotonin 1A receptor agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study was to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). METHOD: 12 patients (mean +/- SD age = 46.6 +/- 11.3 years, 66.7% female) with major depressive disorder (MDD) diagnosed by use of the Structured Clinical Interview for DSM-IV-Axis I Disorders, who had failed to experience a clinical response following an adequate trial of an SSRI, were treated with open-label aripiprazole in addition to their SSRI for 8 weeks. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline-endpoint) as measured by the 17-item Hamilton Rating Scale for Depression total score. Data were collected from August 2003 to July 2004. RESULTS: 9/12 (75.0%) patients completed the trial. Using a completer analysis, 5/9 (55.6%) patients were classified as responders. An intent-to-treat (ITT) analysis resulted in 7 responders (58.3%). The overall proportion of remitters was 3/9 (33.3%) using a completer analysis and 5/12 (41.7%) using the ITT analysis. Aripiprazole administration appeared safe, with no severe adverse events observed in any of the study participants. CONCLUSIONS: These results suggest a possible augmentation role for aripiprazole when used in conjunction with SSRIs in SSRI-resistant MDD.

A description of next-step switching versus augmentation practices for outpatients with treatment-resistant major depressive disorder enrolled in an academic specialty clinic.

BACKGROUND: There is a paucity of naturalistic studies from depression specialty clinics describing the next-step (augmentation versus switching) practices of clinicians for outpatients with major depressive disorder (MDD) resistant to an antidepressant trial of adequate dose and duration. METHODS: Eighty-five MDD outpatients enrolled in one of two specialty clinics, who had not achieved remission after a first adequate prospective antidepressant trial conducted at the clinic underwent either augmentation (n = 36) or switching (n=49) of their antidepressant regimen. Outcome was defined with the use of the Clinical Global Impressions (CGI) Scale. RESULTS: Nonresponders (CGI-I>3) following the first antidepressant trial were more likely to have their treatment switched than patients who experienced incomplete response (CGI-I<4, CGI-S>1) (67.2% versus 28.5%, p = 0.001). Incomplete responders during the first trial who went on to receive augmentation had higher remission rates (60.0% versus 0%, p=0.01), lower endpoint depression severity scores (1.8 +/- 1.1 versus 3.3 +/- 0.8, p = 0.01) and greater clinical improvement scores (1.6 +/- 1.1 versus 3.0 +/- 0.0, p=0.03) than incomplete responders who had their antidepressant regimen switched. Although nonresponders to the first treatment who were switched experienced greater symptom improvement than nonresponders who were augmented (2.7 +/- 1.1 versus 3.4 +/- 1.2, p=0.03), there was no significant difference (p>0.05) between these two groups with respect to remission rates (18.6% versus 14.2%, respectively) and endpoint depressive severity (3.0 +/- 1.4 versus 3.4 +/- 1.4, respectively). CONCLUSIONS: In this nonrandomized, naturalistic treatment setting, nonresponders to an adequate, prospective antidepressant trial were more likely to have their antidepressant regimen switched, while patients with incomplete response during the first trial were more likely to have their regimen augmented. In addition, patients with incomplete response who had their treatment augmented had better outcome than patients with incomplete response who had their treatment switched.

Somatic symptoms as predictors of time to onset of response to fluoxetine in major depressive disorder.

OBJECTIVE: In the present study we assessed the relationship between somatic symptoms and the time to onset of clinical response to fluoxetine in patients with major depressive disorder (MDD). METHOD: 87 outpatients (mean age = 41.4 +/- 10.2 years; 59.8% women) with DSM-III-R MDD who had sustained acute response to fluoxetine completed the Symptom Questionnaire (SQ) at baseline. Onset of response was defined as a 30% decrease in the total score for the 17-item Hamilton Rating Scale for Depression that led to a 50% decrease by week 8. With the use of 2 separate multiple regressions, controlling for the severity of depression at baseline, we then assessed the relationship between the number of somatic symptoms as assessed by the SQ subscale for somatic symptoms (SQ-SS) and both the time to onset of clinical response and the time to clinical response. The study was conducted between November 1992 and January 1999. RESULTS: A greater number of somatic symptoms at baseline predicted a greater amount of time to onset of clinical response to fluoxetine (p =.0233). The relationship between SQ-SS scores and time to response was not found to be statistically significant (p >.05). CONCLUSION: Somatic symptoms of depression were found to be associated with a delayed onset of antidepressant response to fluoxetine in MDD.

Ziprasidone augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder.

BACKGROUND: Due to their favorable side-effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Ziprasidone, an atypical antipsychotic agent with strong 5-HT(1A) agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study is to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). METHOD: Twenty patients with major depressive disorder (MDD) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002. MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline to endpoint), as measured by the HAM-D-17 total score. RESULTS: Thirteen of 20 patients (65.0%) completed the trial. Using a completer analysis, 8 patients (61.5%) were classified as responders. An intent-to-treat (ITT) analysis resulted in 10 responders (50.0%). The overall proportion of remitters was 5 of 13 (38.5%) using a completer analysis and 5 of 20 (25.0%) using the ITT analysis. Ziprasidone administration appeared to be safe, with no clinically significant QTc prolongation or severe adverse events observed in any of the study participants. CONCLUSION: These results suggest a possible augmentation role for ziprasidone when used in conjunction with SSRIs in SSRI-resistant MDD.

Psychiatric comorbidity as a predictor of clinical response to nortriptyline in treatment-resistant major depressive disorder.

BACKGROUND: A number of studies of major depressive disorder suggest that psychiatric co-morbidity may contribute to treatment resistance. The purpose of this study was to test whether the presence of comorbid Axis I and Axis II disorders predicts clinical response to an open trial of nor-triptyline among patients with treatment-resistant depression. METHOD: Ninety-two outpatients with treatment-resistant DSM-III-R major depressive disorder were enrolled in a 6-week open trial of nor-triptyline (Nov. 1992-Jan. 1999). The presence of comorbid Axis I and Axis II disorders was established at baseline with the use of the Structured Clinical Interview for DSM-III-R. Chi-square analyses were used to test Axis I or Axis II co-morbid conditions as a predictor of clinical response to nortriptyline. RESULTS: Thirty-nine patients (42.4%) responded to nortriptyline. The presence of avoidant personality disorder (p <.01) predicted poorer response to nortriptyline. The response rate was 16.7% for patients with and 48.6% for patients without comorbid avoidant personality disorder. No other comorbid diagnoses were found to predict clinical response in a statistically significant manner. CONCLUSION: The presence of avoidant personality disorder conferred a poorer prognosis in treatment-resistant depression patients treated with nortriptyline.

Prevention of relapse and recurrence in depression: the role of long-term pharmacotherapy and psychotherapy.

Major depressive disorder is a chronic disorder, frequently characterized by relapses and recurrences. One of the major risk factors for additional episodes of depression is the presence of residual symptoms that persist after a depressive episode ends; these residual symptoms tend to progress to another depressive episode. Although relapse or recurrence may be prevented with long-term pharmacotherapy, this approach is recommended only for patients at high risk of relapse or recurrence. Patients not at high risk who are effectively treated to full remission have a substantially lower risk of developing another depressive episode. In addition, psychotherapy, alone or combined with medication, has been shown to be effective in preventing further episodes of depression.

Early-onset depression and the emotional and behavioral characteristics of offspring.

We compared the emotional and behavioral characteristics of offspring of parents with early-onset depression and the offspring of parents with late-onset depression. Forty-three parents who met criteria for major depressive disorder (MDD) completed the Achenbach Child Behavior Checklist-Parent Report Version (CBCL) for a birth child (n=43, age range 6-17 years). Parents were classified as having either early SD onset (<19 years) or late-onset (> or = 19 years) MDD based on responses gathered during the SCID-P interview. Unpaired t-tests were used to compare the two offspring groups on CBCL clinical and competency scales. Chi-square analyses and unpaired t-tests were used to compare the two parent groups on demographic and clinical features. Offspring of parents with early-onset depression scored significantly higher on the majority of the CBCL clinical scale scores when compared with offspring of parents with late-onset depression, rated as exhibiting higher levels of the characteristics measured: withdrawn, anxious/depressed, social problems, thought problems, attention problems, delinquent behavior, and aggressive behavior. Additionally, this group had a significantly higher total T score (a global measure of psychopathology) and significantly lower social functioning. Children of parents with early-onset depression may be at higher risk for behavioral and emotional problems than offspring of parents with late-onset depression. This finding may be significant in uncovering sources of vulnerability and formulating intervention strategies for offspring of depressed parents.

Elevated cholesterol levels associated with nonresponse to fluoxetine treatment in major depressive disorder.

Previous studies have suggested that patients with major depressive disorder may have lower cholesterol levels compared to healthy controls. The purpose of this study was to examine the relationship between pretreatment serum cholesterol levels and clinical response to treatment with fluoxetine among outpatients with major depression. Three hundred and twenty-two depressed outpatients meeting DSM-III-R criteria for major depressive disorder were enrolled in an 8-week, fixed-dose, open trial of fluoxetine 20 mg/day. Nonfasting serum cholesterol levels were obtained for all patients before starting fluoxetine. All patients were drug free for a minimum of 2 weeks prior to the onset of the study. Clinical response was defined as a 50% or greater decrease in the 17-item Hamilton Rating Scale for Depression (HAM-D-17) score at endpoint compared to baseline. Cholesterol levels were classified as either elevated (defined as a level equal to or greater than 200 mg/dL) or nonelevated (defined as a level less than 200 mg/dL). Among the 322 outpatients, 51.6% were classified as having elevated and 48.4% as having nonelevated cholesterol levels at baseline (mean cholesterol level 238.6 +/- 33.4 mg/dL vs. 170.4 +/- 22.2 mg/dL, respectively). Depressed patients with elevated cholesterol levels did not significantly differ in gender ratio but were significantly older than depressed patients with nonelevated cholesterol levels (P <.0001). After adjusting for age, gender, and Body Mass Index (BMI), depressed patients with elevated cholesterol levels were significantly more likely to be nonresponders to fluoxetine treatment than were depressed patients with nonelevated cholesterol levels (P < 0.05). Elevated serum cholesterol levels appear to be associated with poorer response to fluoxetine treatment. Further studies are needed to confirm our findings.

Body dysmorphic disorder in outpatients with major depression.

BACKGROUND: Body dysmorphic disorder (BDD) is a distressing and impairing preoccupation with an imagined or slight defect in appearance, with depression as its most frequent comorbid condition. The purpose of this study was to evaluate the rate of BDD in a cohort of consecutive outpatients with typical and atypical major depressive disorder. METHODS: Three hundred and fifty consecutive outpatient subjects with major depression who entered an antidepressant treatment study were evaluated drug-free with the SCID-P, SCID-II, a diagnostic module for BDD, and other measures. Depressed subjects with comorbid BDD were compared to those without BDD with regard to demographics, course of depression, comorbid conditions, and other relevant variables. RESULTS: Twenty-eight (8.0%) subjects had a lifetime history of BDD and 23 (6.6%) had current BDD. Those with comorbid lifetime BDD had an earlier age of onset of depression and longer duration of the current episode, but not a greater number of depressive episodes or greater severity of depression. Subjects with and without BDD were similar with respect to age, gender, and marital status. There was a higher rate of lifetime and current BDD in subjects with atypical depression than in those with non-atypical depression (14.4% compared to 5.1%; chi2 = 6.63; P = 0.01: 11.6% vs. 4.1%; chi2 = 7.02; P = 0.02). Subjects with BDD also had higher rates of social phobia, any eating disorder, and any somatoform disorder but not obsessive compulsive disorder. They also had higher rates of avoidant, histrionic, and dependent personality disorders. LIMITATIONS: As we did not specifically examine bipolar spectrum conditions, the present study cannot address to what extent BDD is comorbid with Bipolar-II disorder. CONCLUSIONS: BDD is frequently comorbid with major depression, is associated with an earlier age of onset of depression and longer duration of depressive episodes, and is found more frequently with atypical than non-atypical depression.

The pharmacologic management of SSRI-induced side effects: a survey of psychiatrists.

Despite the superior side effect profile of the newer antidepressants over the tricyclics and monoamine oxidase inhibitors, all newer antidepressants are associated with a wide array of side effects. Clinicians are constantly confronted with the challenge of managing these side effects in the context of minimal research to prove one management strategy is more effective than another. The purpose of this study was to examine prescribing practices regarding the management of SSRI-associated side effects in a sample of psychiatrists attending a psychopharmacology review course. A total of 439 out of 800 clinicians (55%) attending a psychopharmacology review course responded to our questionnaire that was given prior to beginning the review course, though not all respondents answered all four items on the questionnaire. Among these items were questions designed to assess clinician preference for the management of SSRI-induced side effects. As a treatment for SSRI-induced sexual dysfunction, 43% (143/330) chose adding bupropion, while 36% (120/330) opted to switch agents as their first choice; for SSRI-induced insomnia, 78% (264/326) chose adding trazodone. Switching agents was the first choice of 61% (214/353) of clinicians for managing SSRI-induced agitation, 93% (339/363) for managing SSRI-associated weight gain. In an effort to manage most SSRI-associated side effects (with the exception of sexual dysfunction and insomnia), the majority of the clinicians responding to our survey opted to switch agents rather than add a specific medication to the existing SSRI. In our opinion, this practice may reflect the relative lack of research studies on the role of adjunctive treatments in the management of SSRI-induced side effects and/or the tendency to favor monotherapy over polypharmacy.