Controversy exists as to whether women with depression respond better to selective serotonin reuptake inhibitors (SSRIs) than men. The purpose of this report was to determine whether men and women differ in their responses to treatment with the SSRI citalopram using a large sample of real world patients from primary and psychiatric specialty care settings.
As part of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 2876 participants were treated with citalopram for up to 12-14 weeks. Baseline demographic and clinical characteristics and outcomes were gathered and compared between men and women.
At baseline, women were younger, had more severe depressive symptoms and were more likely to have: early onset; previous suicide attempt(s); a family history of depression, alcohol abuse or drug abuse; atypical symptom features; and one or more of several concurrent psychiatric disorders. Despite greater baseline severity and more Axis I comorbidities, women were more likely to reach remission and response with citalopram than men.
Women have a better response to the SSRI citalopram than men, which may be due to sex-specific biological differences particularly in serotonergic systems.
antidepressants; gender differences; estradiol; women's health; depression
Nine DSM-IV-TR criterion symptom domains are evaluated to diagnose major depressive disorder (MDD). The Quick Inventory of Depressive Symptomatology (QIDS) provides an efficient assessment of these domains and is available as a clinician rating (QIDS-C16), a self-report (QIDS-SR16), and in an automated, interactive voice response (IVR) (QIDS-IVR16) telephone system. This report compares the performance of these three versions of the QIDS and the 17-item Hamilton Rating Scale for Depression (HRSD17).
Data were acquired at baseline and exit from the first treatment step (citalopram) in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Outpatients with nonpsychotic MDD who completed all four ratings within ±2 days were identified from the first 1500 STAR*D subjects. Both item response theory and classical test theory analyses were conducted.
The three methods for obtaining QIDS data produced consistent findings regarding relationships between the nine symptom domains and overall depression, demonstrating interchangeability among the three methods. The HRSD17, while generally satisfactory, rarely utilized the full range of item scores, and evidence suggested multidimensional measurement properties.
In nonpsychotic MDD outpatients without overt cognitive impairment, clinician assessment of depression severity using either the QIDS-C16 or HRSD17 may be successfully replaced by either the self-report or IVR version of the QIDS.
Quick Inventory of Depressive Symptomatology; Inventory of Depressive Symptomatology; item response theory; Samejima graded response model; depressive symptoms
Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD who responded without remitting after up to 12 weeks of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Response was defined as 50% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptomatology—Self-Report (QIDS-SR16) by treatment exit, and remission as a final QIDS-SR16 of less than 6. Residual symptom domains and individual symptoms were based on the QIDS-SR16 and classified as either persisting from baseline or emerging during treatment. Most responders who did not remit endorsed approximately 5 residual symptom domains and 6 to 7 residual depressive symptoms. The most common domains were insomnia (94.6%), sad mood (70.8%), and decreased concentration (69.6%). The most common individual symptoms were midnocturnal insomnia (79.0%), sad mood (70.8%), and decreased concentration/decision making (69.6%). The most common treatment-emergent symptoms were midnocturnal insomnia (51.4%) and decreased general interest (40.0%). The most common persistent symptoms were midnocturnal insomnia (81.6%), sad mood (70.8%), and decreased concentration/decision making (70.6%). Suicidal ideation was the least common treatment-emergent symptom (0.7%) and the least common persistent residual symptom (17.1%). These findings suggest that depressed outpatients who respond by 50% without remitting to citalopram treatment have a broad range of residual symptoms. Individualized treatments are warranted to specifically address each patient's residual depressive symptoms.
depression; STAR*D; residual; symptoms; treatment response
Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have previously described association between treatment emergent suicidal ideation (TESI) and markers in genes encoding the glutamate receptors GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high-risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. A clinically-representative cohort of outpatients with non-psychotic major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 90 white participants who developed TESI and a gender and race matched equal number of treated participants who denied any suicidal ideas were genotyped with 109,365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. One marker was found to be associated with TESI in this sample at the experiment-wide adjusted p<0.05 level (marker rs11628713, allelic p= 6.2 × 10-7, OR = 4.7, permutation p=0.01). A second marker was associated at the experiment-wide adjusted p=0.06 level (rs10903034, allelic p = 3.02× 10-6, OR = 2.7, permutation p=0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. Together with our previous report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event.
treatment-emergent suicidal ideation; TESI; pharmacogenetics; citalopram; antidepressant; major depression; SSRI; STAR*D; genome-wide
Irritability is common during major depressive episodes, but its clinical significance and overlap with symptoms of anxiety or bipolar disorder remains unclear. We examined clinical correlates of irritability in a confirmatory cohort of Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study participants with major depressive disorder (MDD).
Logistic regression was used to identify features associated with presence of irritability on the clinician-rated Inventory of Depressive Symptomatology.
Of 2,307 study participants, 1067(46%) reported irritability at least half the time during the preceding week; they were more likely to be female, to be younger, to experience greater depression severity and anxiety, and to report poorer quality of life, prior suicide attempts, and suicidal ideation. Bipolar spectrum features were not more common among those with irritability.
Irritable depression is not a distinct subtype of MDD, but irritability is associated with greater overall severity, anxiety comorbidity, and suicidality.
major depressive disorder; bipolar disorder; diagnosis; irritability; anger; suicide
Both the 17-item Hamilton Rating Scale for Depression (HRSD17) and 30-item Inventory of Depressive Symptomatology – Clinician-rated (IDS-C30) contain a subscale that assesses anxious symptoms. We used classical test theory and item response theory methods to assess and compare the psychometric properties of the two anxiety subscales (HRSDANX and IDS-CANX) in a large sample (N = 3453) of outpatients with non-psychotic major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Approximately 48% of evaluable participants had at least one concurrent anxiety disorder by the self-report Psychiatric Diagnostic Screening Questionnaire (PDSQ). The HRSDANX and IDS-CANX were highly correlated (r = 0.75) and both had moderate internal consistency given their limited number of items (HRSDANX Cronbach’s alpha = 0.48; IDS-CANX Cronbach’s alpha = 0.58). The optimal threshold for ascribing the presence/absence of anxious features was found at a total score of eight or nine for the HRSDANX and seven or eight for the IDS-CANX. It would seem beneficial to delete item 17 (loss of insight) from the HRSDANX as it negatively correlated with the scale’s total score. Both the HRSDANX and IDS-CANX subscales have acceptable psychometric properties and can be used to identify anxious features for clinical or research purposes.
depression; anxiety; rating scales; STAR*D; measurement-based care
Hormone-based contraceptives affect mood in healthy women or in women with Premenstrual Dysphoric Disorder. No study has yet examined their association with mood in women with major depressive disorder (MDD). The purpose of this study was to determine whether estrogen-progestin combination or progestin-only contraceptives are associated with depression severity, function and quality of life, or general medical or psychiatric comorbidity in women with MDD.
This analysis focused on a large population of female outpatients less than 40 years of age with non-psychotic MDD who were treated in 18 primary and 23 psychiatric care settings across the United States, using data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Baseline demographic and clinical information was gathered and compared between three groups based on hormonal use: combination (estrogen-progestin)(N=232), progestin-only (N=58), and no hormone treatment (N=948).
Caucasians were significantly more likely to use combined hormone contraception. Women on progestin-only had significantly more general medical comorbidities; greater hypersomnia, weight gain and gastrointestinal symptoms; and worse physical functioning than women in either of the other groups. Those on combined hormone contraception were significantly less depressed than those with no hormone treatment by the 16-item Quick Inventory of Depressive Symptomatology - Self-Rated. The combined hormone group also demonstrated better physical functioning and less obsessive-compulsive disorder comorbidity than either of the other groups.
Synthetic estrogen and progestins may influence depressive and physical symptoms in depressed women.
Estradiol; Progesterone; Major Depression; Mood symptoms; Oral contraceptives; Norplant
Whether the acute outcomes of major depressive disorder (MDD) treated in primary (PC) or specialty care (SC) settings are different is unknown.
To compare the treatment and outcomes for depressed outpatients treated in primary versus specialty settings with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a broadly inclusive effectiveness trial.
Open clinical trial with citalopram for up to 14 weeks at 18 primary and 23 specialty sites. Participants received measurement-based care with 5 recommended treatment visits, manualized pharmacotherapy, ongoing support and guidance by a clinical research coordinator, the use of structured evaluation of depressive symptoms and side effects at each visit, and a centralized treatment monitoring and feedback system.
A total of 2,876 previously established outpatients in primary (n = 1091) or specialty (n = 1785) with nonpsychotic depression who had at least 1 post-baseline measure.
Measurements and Main Results
Remission (Hamilton Depression Rating Scale for Depression [Hamilton] or 16-item Quick Inventory of Depressive Symptomatology-Self-Rated [QIDS-SR16]); response (QIDS-SR16); time to first remission (QIDS-SR16). Remission rates by Hamilton (26.6% PC vs 28.0% SC, p = .40) and by QIDS-SR16 (32.5% PC vs 33.1% SC, p = .78) and response rates by QIDS-SR16 (45.7% PC vs 47.6% SC, p = .33) were not different. For those who reached remission or response at exit, the time to remission (6.2 weeks PC vs 6.9 weeks SC, p = .12) and to response (5.5 weeks PC vs 5.4 weeks SC, p = .97) did not differ by setting.
Identical remission and response rates can be achieved in primary and specialty settings when identical care is provided.
primary care; depression; clinical trial; outcomes
Evidence suggests that comorbid depression influences the outcome of cognitive-behavioral treatment for patients presenting with social phobia. Little is known, however, about the influence of comorbid social phobia on the response to cognitive therapy (CT) for depression among adults presenting with recurrent major depressive disorder (MDD). These analyses seek to clarify this relationship.
Patients (N = 156) with recurrent DSM-IV MDD entered CT (20% also met DSM-IV criteria for social phobia). Every week during the course of CT, clinicians assessed depressive symptoms and patients completed self-report instruments measuring severity of depression and anxiety.
At presentation, outpatients with comorbid social phobia reported greater levels of depressive symptoms and clinicians rated their impairment as more severe, compared to their counterparts without social phobia. Patients with or without comorbid social phobia did not differ significantly in (1) attrition rates; (2) response or sustained remission rates; (3) time to response or sustained remission; or (4) rate of improvement in symptoms of depression or anxiety.
The lack of domain-specific measures limits inference with respect to the improvements in social anxiety that occur with CT of depression.
These findings introduce the hypothesis that CT for depression may be flexible enough to treat the depressive symptoms of patients presenting with MDD who also suffer from social phobia.
Social Phobia; Social Anxiety Disorder; Major Depressive Disorder; Comorbidity; Cognitive Therapy; Treatment Outcome
Women have a higher prevalence of Major Depressive Disorder (MDD) and report more severe depressive symptoms than men. Several studies have suggested that gender differences in depression may occur because women report higher levels of somatic symptoms than men. Those studies, however, have not controlled or matched for non-somatic symptoms. The objective of this study was to examine if women report relatively more somatic symptoms than men matched on cognitive/affective symptoms.
Male and female patients receiving treatment for MDD in outpatient psychiatric clinics in New Jersey and Pennsylvania, USA were matched on Beck Depression Inventory-II (BDI-II) cognitive/affective symptom scores. Male and female BDI-II somatic symptom scores were compared using independent samples 2-tailed t-tests.
Of 472 male and 1,026 female patients, there were 470 male patients (mean age = 40.1 years, SD = 15.1) and 470 female patients (mean age = 43.1 years, SD = 17.2) successfully matched on BDI-II cognitive/affective symptom scores. Somatic symptoms accounted for 35% of total BDI-II scores for male patients versus 38% for matched female patients. Female patients had somatic symptom scores on average 1.3 points higher than males (p<.001), equivalent to 4% of the total BDI-II scores of female patients. Only 5% of male patients and 7% of female patients scored 2 or higher on all BDI-II somatic symptom items.
Gender differences in somatic scores were very small. Thus, differences in the experience and reporting of somatic symptoms would not likely explain gender differences in depression rates and symptom severity.
To describe how alcohol use disorders (AUDs) affect women, focusing on gender-specific implications for primary care physicians (PCPs).
An overview of literature from 1966 to 2000 identified by a medline, PsychINFO and HealthSTAR/Ovid Healthstar database search using key words “women,”“alcohol” and “alcoholism.”
MEASUREMENTS AND MAIN RESULTS
Although the prevalence of AUDs is greater in men than in women, women with AUDs are more likely to seek help, but less likely to be identified by their physicians. Psychiatric comorbidities (especially depression and eating disorders) are more common in women with AUDs than in men with AUDs. A past history of sexual and/or physical abuse places a woman at increased risk for AUDs. Women have a greater sensitivity to alcohol, have an accelerated progression from alcohol toxicity, and have increased mortality at lower levels of consumption compared to men. Women and men who are light-to-moderate drinkers have lower coronary artery disease mortality than do abstainers or heavy drinkers. Risk of breast cancer is increased in women who drink ≥1 drinks daily. Common barriers to treatment include: fear of abandonment by partner; fear of loss of children; and financial dependency. Brief interventions have been shown to be effective in reduction of alcohol consumption in women with at-risk drinking. It is unclear if women-only treatment programs improve outcomes.
PCPs should be alert to gender-specific differences for women with AUDs.
alcoholism; female; primary care; gender effects
The purpose of this study was to determine whether there are differences in depression characteristics among premenopausal, perimenopausal, and postmenopausal women with major depressive disorder. This study also evaluated these differences between postmenopausal women with major depressive disorder who are taking and not taking hormone therapy.
Analyses conducted with data from the Sequenced Treatment Alternatives to Relieve Depression study focused on female outpatients with non-psychotic major depressive disorder seeking treatment in 41 primary or psychiatric care settings across the United States. Baseline demographic and clinical characteristics were compared among women not taking hormone therapy who were premenopausal (N=950), perimenopausal (N=380), or postmenopausal (N=562). These comparisons were also made between postmenopausal women (n=768) taking (N=171) or not taking (N=562) hormone therapy.
After adjusting for sociodemographic and clinical baseline differences, premenopausal women were more likely to present with irritability than either peri- or postmenopausal women, and were more likely to have decreased appetite and less likely to have early morning insomnia than perimenopausal women. Postmenopausal women were more likely to have suicidal ideation and poorer physical functioning than either of the other groups, and were more likely to have sympathetic arousal and gastrointestinal symptoms than premenopausal women. After adjusting for baseline differences, postmenopausal women taking hormone therapy had better physical functioning, fewer melancholic features, less sympathetic arousal, and more lack of involvement in activities than women not taking hormone therapy.
Menopausal status and postmenopausal use of hormone therapy may influence the clinical presentation of major depressive episodes in women.
menopause; hormone therapy; depression; major depressive disorder
Major depressive disorder (MDD) is an often chronic, recurrent illness affecting large numbers of the general population. In recent years, the goal of treatment for MDD has moved from mere symptomatic response to that of full remission (ie, minimal/no residual symptoms). The recent Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial stewed that even with systematic measurement-based treatment, approximately one third of patients reach full remission after one treatment trial, with only two thirds reaching remission after four treatment trials. Treatment-resistant depression (TRD) is therefore a common problem in the treatment of MDD, with 60% to 70% of all patients meeting the criteria for TRD, Given the huge burden of major depressive illness, the low rate of full recovery remains suboptimal. The following article reports on some current treatment strategies available to improve rates of, and to sustain, remission in MDD.
remission; treatment-resistant depression; function
Menopausal status and use of hormonal contraception or menopausal hormone therapy (HT) may affect treatment response to selective serotonin reuptake inhibitors (SSRIs). This report evaluates whether menopausal status and use of hormonal contraceptives or menopausal HT affect outcome in women treated with citalopram.
In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 896 premenopausal and 544 postmenopausal women were treated with citalopram for 12–14 weeks. Baseline demographic and clinical characteristics were used in adjusted analysis of the effect of menopausal status and use of hormonal contraceptives or menopausal HT on outcomes. Remission was defined as final Hamilton Rating Scale for Depression-17 (HRSD17) ≤7 or Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) score ≤5 and response as ≥50% decrease from the baseline QIDS-SR16 score.
Premenopausal and postmenopausal women differed in multiple clinical and demographic baseline variables but did not differ in response or remission rates. Premenopausal women taking hormonal contraceptives had significantly greater unadjusted remission rates on the HRSD17 and the QIDS-SR16 than women not taking contraception. Response and remission rates were not different between postmenopausal women taking vs. not taking HT. Adjusted results showed no significant difference in any outcome measure across menopause status in women who were not taking contraception/HT. There were no significant differences in adjusted results across HT status in premenopausal or postmenopausal women.
In this study, citalopram treatment outcome was not affected by menopausal status. Hormonal contraceptives and HT also did not affect probability of good outcome.
At least three randomized, placebo controlled, double blind studies support the efficacy of computerized Attention Modification Programs (AMP) in reducing symptoms of anxiety in patients diagnosed with an anxiety disorder. In this study we examined patient characteristics that predicted response to AMP in a large sample of individuals diagnosed with Generalized Social Phobia (GSP).
The sample comprised 112 individuals seeking treatment for GSP who completed a randomized clinical trial comparing AMP (n = 55) to a placebo condition (i.e., Attention Control Condition, ACC, n = 57). We examined the following domains of baseline predictors of treatment response: (1) demographic characteristics (gender, age, ethnicity, years of education), (2) clinical characteristics (Axis I comorbidity, trait anxiety, depression), and (3) cognitive disturbance factors (attentional bias for social threat, social interpretation bias).
Results revealed that ethnicity predicted treatment response across both conditions: Participants who self-identified as non-Caucasian displayed better overall response compared to Caucasians. The only prescriptive variable to emerge was attentional bias for social threat at pre-assessment. Specifically, participants in the AMP group who exhibited larger attentional bias scores displayed significantly greater reductions in clinician-rated social anxiety symptoms relative to their counterparts in the ACC group.
These results suggest that AMP may be targeted to individuals most likely to benefit from it.
Social Phobia; Attention; Predictors; Treatment; Information Processing
This study examines the structure of the Personality Belief Questionnaire (PBQ), a self-report instrument designed to assess dysfunctional beliefs associated with personality pathology, as proposed by the cognitive theory of personality dysfunction.
The PBQ was examined using exploratory factor analysis with responses from 438 depressed outpatients, and confirmatory factor analysis with responses from 683 treatment-seeking psychiatric outpatients. All participants were assessed for personality disorder using a standard clinical interview. The validity of the resulting factor structure was assessed in the combined sample (N=1121) by examining PBQ scores for patients with and without personality disorder diagnoses.
Exploratory and confirmatory analyses converged to indicate that the PBQ is best described by 7 empirically identified factors: 6 assess dysfunctional beliefs associated with forms of personality pathology recognized in DSM-IV. Validity analyses revealed that those diagnosed with a personality disorder evidenced a higher average score on all factors, relative to those without these disorders. Subsets of patients diagnosed with specific DSM-IV personality disorders scored higher, on average, on the factor associated with their respective diagnosis, relative to all other factors.
The pattern of results has implications for the conceptualization of personality pathology. To our knowledge, no formal diagnostic or assessment system has yet systematically incorporated the role of dysfunctional beliefs into its description of personality pathology. The identification of dysfunctional beliefs may not only aid in case conceptualization, but may provide unique targets for psychological treatment. Recommendations for future personality pathology assessment systems are provided.
The higher prevalence and cost of depression for women compared with men and the possible gender differences in treatment response demand the inclusion of women in clinical trials of depression treatments. The 1993 National Institutes of Health (NIH) Revitalization Act set a new standard, requiring investigators to consider the inclusion of women and analyze outcomes by gender, yet compliance with these standards in depression research has not been examined systematically. The purpose of this study is to examine the inclusion of women and gender-specific analyses in recent randomized clinical trials (RCTs) for depression.
RCTs were identified through a MEDLINE search for trials published between January 1 and December 31, 2007, and a Clinicaltrials.gov search of self-identified interventional studies to treat depression.
Of the 150 RCTs for depression published in 2007, 15% did not report the gender composition of their sample, 50% of studies did not analyze outcomes by gender, and 12% controlled for gender but did not analyze for gender differences. Of the 768 trials reviewed on Clinicaltrials.gov, 89% reported recruiting male and female participants, yet <1% reported an intention to analyze results by gender.
Many recent studies of depression treatments include women but do not examine outcomes by gender. Understanding how women differ from men in response to treatment is critical for enhancing treatment efficacy for the greatest number of adults with depression.
Psychotic major depression (PMD) is a severe mental disorder characterized by high levels of illness severity, chronicity, impairment, and treatment resistance. However, most past research on PMD has been conducted in inpatient hospital samples, and relatively little is known about PMD patients presenting for treatment in the community specifically.
In this study, we examined the prevalence and clinical characteristics of PMD in a large sample (n = 2,500) of treatment-seeking outpatients who were administered structured clinical interviews by trained diagnosticians.
Of the patients diagnosed with major depression, 5.3% had psychotic features. PMD patients were more likely to be members of a racial/ethnic minority and to have lower educational attainment compared to those with nonpsychotic major depression. In addition, PMD patients were found to have greater current depression severity, suicidal ideation, and social and work impairment. These patients also were more likely to have histories of suicide attempts and psychiatric hospitalizations, to report an earlier age of illness onset, and to meet criteria for chronic depression. In terms of psychiatric comorbidity, PMD patients had higher rates of certain anxiety disorders as well as more somatoform and cluster A personality disorders.
Results indicated that PMD was present in a relatively small percentage of treatment-seeking outpatients but was associated with disproportionately high levels of severity and impairment. Similarities and differences between the current findings and those from past research are discussed, including clinical implications for the identification and treatment of PMD in routine practice settings.
major depression; psychotic depression; hallucinations; delusions; outpatient psychiatry
The Hospital Anxiety and Depression Scale (HADS) is a common screening instrument excluding somatic symptoms of depression and anxiety, but previous studies have reported inconsistencies of its factor structure. The construct validity of the Japanese version of the HADS has yet to be reported. To examine the factor structure of the HADS in a Japanese population is needed.
Exploratory and confirmatory factor analyses were conducted in the combined data of 408 psychiatric outpatients and 1069 undergraduate students. The data pool was randomly split in half for a cross validation. An exploratory factor analysis was performed on one half of the data, and the fitness of the plausible model was examined in the other half of the data using a confirmatory factor analysis. Simultaneous multi-group analyses between the subgroups (outpatients vs. students, and men vs. women) were subsequently conducted.
A two-factor model where items 6 and 7 had dual loadings was supported. These factors were interpreted as reflecting anxiety and depression. Item 10 showed low contributions to both of the factors. Simultaneous multi-group analyses indicated a factor pattern stability across the subgroups.
The Japanese version of HADS indicated good factorial validity in our samples. However, ambiguous wording of item 7 should be clarified in future revisions.
A recent study has reported a significant association of variants in phosphodiesterase (PDE) genes with antidepressant treatment outcome in a Mexican American sample (Wong et al. 2006). We set out to investigate these findings in a large sample of patients from the Sequenced Treatment Alternatives for Depression (STAR*D) study. STAR*D is a longitudinal study of antidepressant outcome in depressed outpatients.
We genotyped three single nucleotide polymorphisms (SNPs) in PDE11A (rs1880916), PDE1A (rs1549870), and PDE9A (rs729861) for replication and we also report three additional SNPs in PDE11A (rs3770016, rs4893975, rs6433687) that had been genotyped for a previous study.
Single marker analysis of remission within the Hispanic subsamples (n = 268) revealed no significant evidence of association with markers in PDE11A, PDE9A or PDE1A. Additional analyses of remission within the total STAR*D sample (n=1,914) were also largely negative, as were analyses utilizing a narrower definition of remission. Haplotype analyses were performed with the four PDE11A SNPs we genotyped; these also failed to show significant evidence of association in the STAR*D sample.
We could not reproduce the reported association between PDE genes and antidepressant outcome in a sample of subjects comparable to that reported previously. We conclude that PDE11A, PDE9A, and PDE1A are unlikely to play an important role in antidepressant outcome in this sample.
Depression; PDE; STAR*D; pharmacogenetics
It has been suggested that there is a mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with antidepressant response, and poorer outcomes among NSAID-treated patients were reported in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. To attempt to confirm this association in an independent population-based treatment cohort and explore potential confounding variables, the authors examined use of NSAIDs and related medications among 1,528 outpatients in a New England health care system.
Treatment outcomes were classified using a validated machine learning tool applied to electronic medical records. Logistic regression was used to examine the association between medication exposure and treatment outcomes, adjusted for potential confounding variables. To further elucidate confounding and treatment specificity of the observed effects, data from the STAR*D study were reanalyzed.
NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (odds ratio=1.55, 95% CI=1.21–2.00). This association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding; association with outcome was no longer significant in fully adjusted models. Reanalysis of STAR*D results likewise identified an association in NSAIDs but not NSAID-like drugs, with more modest effects persisting after adjustment for potential confounding variables.
These results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding.
Gender differences in patterns and consequences of substance use, treatment-seeking, and motivation to change were examined in two samples of people with serious mental illness (SMI) and comorbid substance use disorders (SUDs): a community sample not currently seeking substance abuse treatment (N = 175) and a treatment-seeking sample (N = 137). In both groups, women and men demonstrated more similarities in the pattern and severity of their substance use than differences. However, treatment-seeking women showed greater readiness to change their substance use. Mental health problems and traumatic experiences may prompt people with SMI and SUD to enter substance abuse treatment, regardless of gender.
dual diagnosis; serious mental illness; gender differences; motivation to change; treatment-seeking
A subset of patients undergoing initial antidepressant treatment experience worsening of symptoms, including thoughts of suicide or suicidal behavior. The present study explores whether this subset of patients is also more likely to experience recurrence or worsening of these symptoms during a second treatment trial with a different antidepressant.
We examined data collected between July 2001 and September 2006 from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a multicenter effectiveness study of outpatients with major depressive disorder diagnosed by a DSM-IV checklist. In that study, subjects who did not remit with citalopram treatment were randomized among next-step treatment options. The main outcome measure for this post hoc analysis, presence of suicidal thoughts and behaviors, was assessed using the suicide item on the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated. Logistic regression was used to examine association between emergence or worsening of these symptoms with the first-step (level 1) citalopram treatment and emergence or worsening with next-step (level 2) pharmacologic or psychosocial treatment, including augmentation with bupropion or buspirone; switch to sertraline, venlafaxine, or bupropion; or addition of or switch to cognitive therapy.
Of 1,240 subjects entering level 2 with a score less than 3 on the suicide item, 102 (8.2%) experienced emergence or worsening of suicidal thoughts or behaviors. Emergence or worsening at level 1 was strongly associated with reemergence or worsening at level 2 (crude OR=4.00 [95% CI, 2.45–6.51], adjusted OR=2.95 [95% CI, 1.76–4.96]). Overall magnitude of risk was similar among next-step pharmacologic augmentation versus switching.
These results suggest that individuals who experience emergence or worsening of suicidal thoughts or behaviors with one antidepressant treatment may warrant closer follow-up during the next-step treatment, as these symptoms may recur regardless of which modality is selected.
The purpose of this study was to investigate the relationships of chronic stress, social undermining, and social support with symptom reduction and remission in depressed patients treated with antidepressant medication (citalopram), and to determine whether these relationships were moderated by ethnicity. A sample of 301 treatment-seeking adult patients with non-psychotic depression, including 169 African-American and 132 Caucasian men and women, were enrolled in an eight week, dose escalation clinical trial. Intent-to-treat analyses indicated that, consistent with expectations, more baseline social support was associated with greater symptom reduction and higher likelihood of remission, especially at higher levels of social undermining. Additionally, increases in social support from baseline to last visit were associated with more symptom reduction and higher likelihood of remission. However, contrary to expectations, higher levels of baseline social undermining were associated with more symptom reduction in Caucasians, but not in African-Americans. Results supported the treatment enhancing effect of available social support at the beginning of treatment and over the course of treatment. Efforts to enhance social support for patients on antidepressants should be considered as part of comprehensive treatment.
antidepressant; depression; ethnicity; psychosocial; stress; social support
To evaluate the associations between indices of caregiving strain, ruminative style, depressive symptoms, and gender among family members of patients with bipolar disorder.
One hundred and fifty primary caregivers of patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) participated in a cross-sectional study to evaluate the role of ruminative style in maintaining depressive symptoms associated with caregiving strain. Patient lifetime diagnosis and current episode status were evaluated by the Affective Disorder Evaluation and the Clinical Monitoring Form. Caregivers were evaluated within 30 days of the patient on measures of family strain, depressive symptoms, and ruminative style.
Men and women did not differ on depression, caregiver strain, or ruminative style scores. Scores suggest an overall mild level of depression and moderate caregiver strain for the sample. Greater caregiver strain was significantly associated (P < 0.05) with rumination and level of depressive symptoms, controlling for patient clinical status and demographic variables. Rumination reduced the apparent association between strain and depression by nearly half. Gender was not significantly associated with depression or rumination.
Rumination helps explain depressive symptoms experienced by both male and female caregivers of patients with bipolar disorder. Interventions for caregivers targeted at decreasing rumination should be considered.
Caregiving strain; bipolar disorder; rumination; depression