Michael A. Gara

A controlled trial of antidepressants in patients with Parkinson disease and depression

Background: Parkinson disease (PD) is a common neurodegenerative disease affecting up to 1 million individuals in the United States. Depression affects up to 50% of these patients and is associated with a variety of poor outcomes for patients and their families. Despite this, there are few evidence-based data to guide clinical care. Methods: An NIH-funded, randomized, controlled trial of paroxetine CR, nortriptyline, and placebo in 52 patients with PD and depression. The primary outcomes were the change in the Hamilton Depression Rating Scale (HAM-D) and the percentage of depression responders at 8 weeks. Results: Nortriptyline was superior to placebo for the change in HAM-D (p < 0.002); paroxetine CR was not. There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks (p < 0.079). Response rates favored nortriptyline (p = 0.024): nortriptyline 53%, paroxetine CR 11%, placebo 24%. In planned contrasts of response rates, nortriptyline was superior to paroxetine CR (p = 0.034). Nortriptyline was also superior to placebo in many of the secondary outcomes, including sleep, anxiety, and social functioning, while paroxetine CR was not. Both active drug treatments were well tolerated. Conclusions: Though relatively modest in size, this is the largest placebo-controlled trial done to date in patients with Parkinson disease (PD) and depression. Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not. When compared directly, nortriptyline produced significantly more responders than did paroxetine CR. The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors. ARR = absolute risk reduction; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; HAM-A = Hamilton Anxiety Scale; HAM-D = Hamilton Depression Rating Scale; MMSE = Mini-Mental State Examination; NNT = number needed to treat; PD = Parkinson disease; PDQ = Parkinson’s Disease Questionnaire; PSQI = Pittsburgh Sleep Quality Index; SCID = Structured Clinical Interview; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant; UPDRS = Unified Parkinson’s Disease Rating Scale.

Cognitive-behavioral therapy for depression in Parkinson's disease: a randomized, controlled trial.

OBJECTIVE Despite the negative effects of depression in Parkinsons disease, there is currently no evidence-based standard of care. The purpose of this study was to examine the efficacy of individually administered cognitive-behavioral therapy (CBT), relative to clinical monitoring (with no new treatment), for depression in this medical population. METHOD Eighty depressed (based on DSM-IV criteria) patients with Parkinsons disease participated in a randomized, controlled trial of CBT relative to clinical monitoring (1:1 ratio) in an academic medical center from April 2007 to July 2010. All patients continued to maintain stable medication regimens under the care of their personal physicians. The 17-item Hamilton Depression Rating Scale (HAM-D) total score was the primary outcome. CBT was modified to meet the unique needs of the Parkinsons disease population and provided for 10 weeks. Assessments were completed by blind raters at baseline and 5 (midpoint), 10 (end of treatment), and 14 weeks (follow-up evaluation) postrandomization. RESULTS The CBT group reported greater reductions in depression (change in HAM-D score) than the clinical monitoring group. At week 10, the mean HAM-D score change was 7.35 for CBT relative to 0.05 for clinical monitoring. CBT was also superior to clinical monitoring on several secondary outcomes (i.e., Beck Depression Inventory scores, anxiety, quality of life, coping, Parkinsons disease symptom ratings). There were more treatment responders in the CBT group than the clinical monitoring group (56% versus 8%, respectively). CONCLUSIONS CBT may be a viable approach for the treatment of depression in Parkinsons disease. Further research is needed to replicate and extend these findings.

Impact of a preventive social problem solving intervention on children's coping with middle-school stressors

Children receiving 1 year or 1/2 year of a preventive social problem solving program in elementary school were compared with each other and with a no-treatment group upon entry into middle school. One year of training was significantly related to reductions in the severity of a variety of middle-school stressors. Most importantly, a clear mediating role for social problem solving (SPS) skills was found. Children lacking in SPS skills were more likely to experience intense stressors; however, possessing the skills was not necessarily predictive of adjustment to stressors. The results are discussed in terms of the implications of this asymmetry and the strong support given to the value of social problem solving as a preventive intervention for children.

Self-complexity, self-evaluation, and depression: An examination of form and content within the self-schema.

Six studies examined the relationship between self-complexity and variables related to self-evaluation. Self-complexity was found to comprise two components: positive self-complexity and negative self-complexity. Positive self-complexity was sensitive to methodological factors, namely, variations in stimulus materials used for self-ratings. Negative self-complexity was relatively stable in the face of different rating stimuli and tasks and was related to trait measures of self-evaluation, psychic distress, and psychopathology. These findings were observed and replicated. Higher negative self-complexity was associated with increases in depression symptoms over time. Higher negative self-complexity also predicted a poorer prognosis and less complete recovery from depression in a clinical sample. Results are discussed in light of related research and possible social-cognitive mechanisms.

Perception of self and other in major depression

Previous research on the nature of person perception in depression has been inconclusive. This investigation differs from earlier studies in that extensive free-response descriptions of other people and self were collected from patients with major depression and from nonpsychiatric control Ss. In comparison with control Ss, depressed patients described fewer positive aspects not only of self but also of parents and significant others and reported more negative aspects of these people. Cluster analysis (HICLAS) also showed that more cognitive differentiation of negative self-perceptions (negative self-complexity) was characteristic of clinical depression. In both control Ss and patients, a positive (or negative) view of self was highly correlated (.85 or more) with a positive (or negative) view of parents and significant others. These correlations were significantly stronger than those between self and less important others.

Effectiveness of a Time-Limited Cognitive Behavior Therapy–Type Intervention Among Primary Care Patients With Medically Unexplained Symptoms

PURPOSE Patients seeking care for medically unexplained physical symptoms pose a major challenge at primary care sites, and there are very few well-accepted and properly evaluated interventions to manage such patients. METHODS We tested the effectiveness of a cognitive behavior therapy (CBT)-type intervention delivered in primary care for patients with medically unexplained physical symptoms. Patients were randomly assigned to receive either the intervention plus a consultation letter or usual clinical care plus a consultation letter. Physical and psychiatric symptoms were assessed at baseline, at the end of treatment, and at a 6-month follow-up. All treatments and assessments took place at the same primary care clinic where patients sought care. RESULTS A significantly greater proportion of patients in the intervention group had physical symptoms rated by clinicians as “very much improved” or “much improved” compared with those in the usual care group (60% vs 25.8%; odds ratio = 4.1; 95% confidence interval, 1.9–8.8; P<.001). The intervention’s effect on unexplained physical symptoms was greatest at treatment completion, led to relief of symptoms in more than one-half of the patients, and persisted months after the intervention, although its effectiveness gradually diminished. The intervention also led to significant improvements in patient-reported levels of physical symptoms, patient-rated severity of physical symptoms, and clinician-rated depression, but these effects were no longer noticeable at follow-up. CONCLUSIONS This time-limited, CBT-type intervention significantly ameliorated unexplained physical complaints of patients seen in primary care and offers an alternative for managing these common and problematic complaints in primary care settings.

DSM-IV Hypochondriasis in Primary Care

The object of this study was to assess the prevalence and correlates of the DSM-IV diagnosis of hypochondriasis in a primary care setting. A large sample (N = 1456) of primary care users was given a structured interview to make diagnoses of mood, anxiety, and somatoform disorders and estimate levels of disability. The prevalence of hypochondriasis (DSM-IV) was about 3%. Patients with this disorder had higher levels of medically unexplained symptoms (abridged somatization) and were more impaired in their physical functioning than patients without the disorder. Of the various psychopathologies examined, major depressive syndromes were the most frequent among patients with hypochondriasis. Interestingly, unlike somatization disorder, hypochondriasis was not related to any demographic factor. Hypochondriasis is a relatively rare condition in primary care that is largely separable from somatization disorder but seems closely intertwined with the more severe depressive syndromes.

Measuring identity multiplicity and intersectionality: Hierarchical Classes Analysis (HICLAS) of sexual, racial, and gender identities

We propose an innovative approach for measuring identity multiplicity and intersectionality—Hierarchical Classes Analysis (HICLAS) of an Assessment of Multiple Identities. This method allows researchers to assess characteristics of individual identities and model implicit interrelationships between multiple identities held by an individual. We found support for the validity of this approach through analysis of sexual, racial, and gender identities among 40 lesbian, gay, or bisexually identified (LGB) participants. As hypothesized, poorer mental health indicators were significantly associated with greater negative valence of sexual identity and greater negative self-complexity in HICLAS. HICLAS also allowed us to discern subgroup differences indicative of intersectionality (e.g., in this LGB sample, more African American participants than White participants showed interconnected sexual and racial identities).

The impact of treatment of depression on quality of life, disability and relapse in patients with Parkinson's disease†

Parkinsons disease (PD) is a common neurodegenerative disease affecting up to one million individuals in the United States. Depression is found in 40 to 50% of these patients and is associated with a variety of poor outcomes for both patients and their families. Despite this, there are few evidence‐based data to guide clinical care. This was an NIH‐funded, randomized, controlled trial of paroxetine, nortriptyline, and placebo. It included an 8 week acute phase and a 16 week blind extension phase. This report details the impact of depression treatment on quality of life (QoL) and disability in the acute and extension phase of this study. Secondary outcomes included relapse, tolerability, safety, and the impact of depression treatment on PD physical functioning. Patients who had improvement in depression, compared with those who did not, had significant gains in measures of QoL and disability (PDQ‐8, P = 0.0001; SF‐36, P = 0.0001) at 8 weeks and maintained their gains in the extension phase. Patients who were on active drug were significantly less likely to relapse in the extension phase than those on placebo (P = 0.041). Though relatively modest in size, this trial provides the first controlled data on the impact of treatment of depression on QoL and disability in PD. It suggests that successfully treating depression in PD leads to important, sustained improvements in these outcomes and that patients who improve on antidepressants are less likely to relapse than are patients who initially improve on placebo.

Influence of Patient Race and Ethnicity on Clinical Assessment in Patients With Affective Disorders

CONTEXT Rates of clinical diagnoses of schizophrenia in African American individuals appear to be elevated compared with other ethnic groups in the United States, contradicting population rates derived from epidemiologic surveys. OBJECTIVE To determine whether African American individuals would continue to exhibit significantly higher rates of clinical diagnoses of schizophrenia, even after controlling for age, sex, income, site, and education, as well as the presence or absence of serious affective disorder, as determined by experts blinded to race and ethnicity. A secondary objective was to determine if a similar pattern occurred in Latino subjects. DESIGN Ethnicity-blinded and -unblinded diagnostic assessments were obtained in 241 African American individuals (mean [SD] age, 34.3 [8.1] years; 57% women), 220 non-Latino white individuals (mean [SD] age, 32.7 [8.5] years; 53% women), and 149 Latino individuals (mean [SD] age, 33.5 [8.0] years; 58% women) at 6 US sites. Logistic regression models were used to determine whether elevated rates of schizophrenia in African American individuals would persist after controlling for various confounding variables including blinded expert consensus diagnoses of serious affective illness. SETTINGS Six academic medical centers across the United States. PARTICIPANTS Six hundred ten psychiatric inpatients and outpatients. MAIN OUTCOME MEASURE Relative odds of unblinded clinical diagnoses of schizophrenia in African American compared with white individuals. RESULTS A significant ethnicity/race effect (χ(2)(2)=10.4, P=.01) was obtained when schizophrenia was narrowly defined, controlling for all other predictors. The odds ratio comparing African American with non-Latino white individuals was significant (odds ratio=2.7; 95% CI, 1.5-5.1). Similar differences between African American and white individuals occurred when schizophrenia was more broadly defined (odds ratio=2.5; 95% CI, 1.4-4.5). African American individuals did not differ significantly from white individuals in overall severity of manic and depressive symptoms but did evidence more severe psychosis. CONCLUSIONS African American individuals exhibited significantly higher rates of clinical diagnoses of schizophrenia than non-Latino white subjects, even after controlling for covariates such as serious affective disorder.