Nonpsychotic Major Depression Research Articles

The response of psychotic-like symptoms to fluoxetine monotherapy in non-psychotic major depressive disorder

Objective: To determine the prevalence of psychotic-like symptoms in non-psychotic major depressive disorder and to monitor the response of these symptoms to monotherapy with fluoxetine. Methods: We reviewed the charts of 384 subjects (54.7% women; mean age 39.9±10), all outpatients diagnosed with non-psychotic major depressive disorder by the Structured Clinical Interview for DSM-IV (SCID), aged 18–65 years, with an initial 17-item Hamilton Depression (HAM-D-17) score of 16 or greater. Subjects were treated openly with fluoxetine 20 mg/day for 8 weeks. Subjects were administered the SCID-II (Structured Clinical Diagnostic Interview for Personality Disorder) prior to entering acute treatment and at the completion of the acute phase of treatment. We monitored the course of psychotic-like symptoms following this course of therapy. Results: 187 subjects endorsed at least one psychotic-like symptom, including not trusting close acquaintances (item 51), picking up hidden meanings (item 52), believing that others were talking about them (item 57), magical thinking (item 60) or unusual perceptual experiences (item 62). None of these patients met criteria for delusional depression as defined by the SCID. Overall response rates were 36.4% for patients who endorsed psychotic-like symptoms, and 53.3% for those who did not endorse psychotic-like symptoms (chi-squared = 11.1, P=0.001). The decrease in psychotic-like symptoms during the course of fluoxetine monotherapy was significant (P<0.05) in both responders and non-responders to treatment. Conclusion: A significant percentage of patients with non-psychotic major depression endorse subtle psychotic-like symptoms, many of which abate during monotherapy with fluoxetine regardless of response of the depressive symptoms.

Depression Outcomes of Spanish- and English-Speaking Hispanic Outpatients in STAR*D

This secondary data analysis from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study compared clinical characteristics and outcome after citalopram treatment for Hispanic outpatients whose language preference was English (N=121) or Spanish (N=74).Data for Hispanic outpatients with nonpsychotic major depression were gathered from two STAR*D regional centers. Participants received citalopram for up to 14 weeks, with dosage adjustments based on routine clinical assessments. Efforts were made to achieve remission with a measurement-based care approach, with adjustments symptoms and side effects.Spanish speakers were older, were more likely to be women, were less educated, had lower income, had more medical burden, and were more likely than English speakers to be seen in primary care rather than in psychiatric clinics. Compared with Spanish speakers, English speakers had more previous suicide attempts and more family history of mood disorders. The groups did not differ in a clinically meaningful way in severity of depression. Before adjustment for baseline differences, Spanish-speaking participants had lower rates of and slower times to remission and response compared with English speakers. After adjustment for baseline variables, these differences were no longer significant. Relapse rates did not differ between groups.Compared with English-speaking Hispanic patients, Spanish-speaking Hispanic patients may have a less robust response to antidepressants. The reasons for this are not clear but may include more disadvantaged social status. The degree to which these results can be generalized to other Hispanic populations or to other non-English-speaking groups remains to be seen.

Depression Outcomes of Spanish- and English-Speaking Hispanic Outpatients in STAR*D

This secondary data analysis from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study compared clinical characteristics and outcome after citalopram treatment for Hispanic outpatients whose language preference was English (N=121) or Spanish (N=74). Data for Hispanic outpatients with nonpsychotic major depression were gathered from two STAR*D regional centers. Participants received citalopram for up to 14 weeks, with dosage adjustments based on routine clinical assessments. Efforts were made to achieve remission with a measurement-based care approach, with adjustments symptoms and side effects. Spanish speakers were older, were more likely to be women, were less educated, had lower income, had more medical burden, and were more likely than English speakers to be seen in primary care rather than in psychiatric clinics. Compared with Spanish speakers, English speakers had more previous suicide attempts and more family history of mood disorders. The groups did not differ in a clinically meaningful way in severity of depression. Before adjustment for baseline differences, Spanish-speaking participants had lower rates of and slower times to remission and response compared with English speakers. After adjustment for baseline variables, these differences were no longer significant. Relapse rates did not differ between groups. Compared with English-speaking Hispanic patients, Spanish-speaking Hispanic patients may have a less robust response to antidepressants. The reasons for this are not clear but may include more disadvantaged social status. The degree to which these results can be generalized to other Hispanic populations or to other non-English-speaking groups remains to be seen.

Prevalence and clinical characteristics of psychotic versus nonpsychotic major depression in a general psychiatric outpatient clinic

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.

Daily Left Prefrontal Repetitive Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: Clinical Predictors of Outcome in a Multisite, Randomized Controlled Clinical Trial

Randomized controlled trials support the antidepressant efficacy of transcranial magnetic stimulation (TMS); however, there is individual variability in the magnitude of response. Examination of response predictors has been hampered by methodological limitations such as small sample sizes and single-site study designs. Data from a multisite sham-controlled trial of the antidepressant efficacy of TMS provided an opportunity to examine predictors of acute outcome. An open-label extension for patients who failed to improve provided the opportunity for confirmatory analysis. Treatment was administered to the left dorsolateral prefrontal cortex at 10 pulses per second, 120% of motor threshold, for a total of 3000 pulses per day. Change on the Montgomery-Asberg Depression Rating Scale after 4 weeks was the primary efficacy outcome. A total of 301 patients with nonpsychotic unipolar major depression at 23 centers were randomized to active or sham TMS. Univariate predictor analyses showed that the degree of prior treatment resistance in the current episode was a predictor of positive treatment outcome in both the controlled study and the open-label extension trial. In the randomized trial, shorter duration of current episode was also associated with a better outcome. In the open-label extension study, absence of anxiety disorder comorbidity was associated with an improved outcome, but duration of current episode was not. The number of prior treatment failures was the strongest predictor for positive response to acute treatment with TMS. Shorter duration of current illness and lack of anxiety comorbidity may also confer an increased likelihood of good antidepressant response to TMS.

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

Objective Patients (30–50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication. Method Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5–3 mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of ⩽10 on the Montgomery–Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire. Results Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR = 3.33, p = .011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS ⩽ 10) compared to 24% of the placebo augmentation group (CMH(1) = 6.48, p = .011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no between-group differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone. Conclusion Augmentation of an antidepressant with risperidone for patients with difficult-to-treat depression leads to more rapid response and a higher remission rate and better quality-of-life.

Is Aripiprazole an Efficacious Adjunct for Unipolar Depression?

Article AbstractLetter to the Editor Sir: As part of a psychiatry residents†journal club, we reviewedthe recently published study by Berman et al. on the efficacyof adjunctive aripiprazole versus adjunctive placebo inpatients with unipolar, nonpsychotic major depression. We identifiedone potential confounding factor, for which we thoughtfurther data might provide some clarification.

Depressive symptom profiles and severity patterns in outpatients with psychotic vs nonpsychotic major depression

Background Previous research suggests that patients with psychotic major depression (PMD) may differ from those with nonpsychotic major depression (NMD) not only in psychotic features but also in their depressive symptom presentation. The present study contrasted the rates and severity of depressive symptoms in outpatients diagnosed with PMD vs NMD. Method The sample consisted of 1112 patients diagnosed with major depression, of which 60 (5.3%) exhibited psychotic features. Depressive symptoms were assessed by trained diagnosticians at intake using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and supplemented by severity items from the Schedule for Affective Disorders and Schizophrenia. Results Patients with PMD were more likely to endorse the presence of weight loss, insomnia, psychomotor agitation, indecisiveness, and suicidality compared with NMD patients. Furthermore, PMD patients showed higher levels of severity on several depressive symptoms, including depressed mood, appetite loss, insomnia, psychomotor disturbances (agitation and retardation), fatigue, worthlessness, guilt, cognitive disturbances (concentration and indecisiveness), hopelessness, and suicidal ideation. The presence of psychomotor disturbance, insomnia, indecisiveness, and suicidal ideation was predictive of diagnostic status even after controlling for the effects of demographic characteristics and other symptoms. Conclusions These findings are consistent with past research suggesting that PMD is characterized by a unique depressive symptom profile in addition to psychotic features and higher levels of overall depression severity. The identification of specific depressive symptoms in addition to delusions/hallucinations that can differentiate PMD vs NMD patients can aid in the early detection of the disorder. These investigations also provide insights into potential treatment targets for this high-risk population.

Changes in Regional Cerebral Blood Flow After Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex in Treatment-Resistant Depression

Changes in Regional Cerebral Blood Flow After Repetitive Transcranial Magnetic Stimulation of the Left Dorsolateral Prefrontal Cortex in Treatment-Resistant Depression

Microstructural White Matter Abnormalities and Remission of Geriatric Depression

White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression. The subjects were nondemented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate. Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions. Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder.

Explaining Patients' Beliefs About the Necessity and Harmfulness of Antidepressants

Patients' beliefs about antidepressants vary widely and probably influence adherence, yet little is known about what underlies such beliefs. This study's objective was to identify the demographic and clinical characteristics that account for patients' beliefs about antidepressants. Participants were 165 patients with unipolar nonpsychotic major depression from primary care and psychiatry clinics who were participating in the baseline phase of a multistaged trial of medication and psychotherapy. Before patients started antidepressants, interview and self-report measures were used to assess treatment beliefs, depression features, and comorbid conditions. Linear multivariate regression was used to identify the strongest correlates of perceived medication necessity and harmfulness after adjusting for age, sex, education, and the random effects of patients within clinical site. Perceived necessity was associated with older age (P <.001), more severe symptoms (P = .03), longer anticipated duration of symptoms (P=.001), and attribution of symptoms to chemical imbalance (P=.005). Perceived harmfulness was highest among patients who had not taken antidepressants before (P = .02), attributed their symptoms to random factors (P=.04), and had a subjectively unclear understanding of depression (P = .003). Neither belief was significantly associated with sex, education, age at first depressive episode, presence of melancholia or anxiety, psychiatric comorbidity, or clinical setting. Skepticism about antidepressants is strongest among younger patients who have never taken antidepressants, view their symptoms as mild and transient, and feel unclear about the factors affecting their depression. Perhaps these patients would benefit the most from adherence promotion focusing on treatment beliefs.

Revised psychopharmacological algorithms for the treatment of mood disorders in Japan

Objective. To revise the psychopharmacology algorithms for the treatment of mood disorders published in 1999 in Japan. Methods. The algorithms were established based on clinical psychopharmacological evidence, the results of a questionnaire survey sent to 200 Japanese psychiatrists, and the consensus of all the research members. Results. Six categorized algorithms have been developed, i.e. mild or moderate major depression, severe non-psychotic major depression, psychotic depression, mania, bipolar depression, and rapid cycling mood disorder. Conclusion. The revised algorithms will be helpful for the treatment of mood disorders in Japan.

Impaired theory of mind in first-episode schizophrenia: comparison with community, university and depressed controls

First order theory of mind, as measured by the ‘Reading the Mind in the Eyes Test’ Revised, is impaired in schizophrenia. However, no study has investigated whether this occurs in first-episode schizophrenia. Also, it is unclear whether such a deficit is specific to schizophrenia, and whether convenience control samples, particularly undergraduate university students, represent valid comparison groups. This study investigated theory of mind ability, measured by the ‘Reading the Mind in the Eyes Test’ Revised, in a group of first-episode schizophrenia outpatients ( n = 13) and three control groups: outpatients with non-psychotic major depression ( n = 14), individuals from the general community ( n = 16) and from an undergraduate university course ( n = 27). The schizophrenia group exhibited significant theory of mind impairments compared to both non-psychiatric control groups but not the depression group. Unexpectedly, the depression group was not significantly impaired compared to the community control group, and the university control group exhibited superior theory of mind ability relative to all three groups. The findings indicate theory of mind deficits in first episode schizophrenia and support the implementation of theory of mind interventions in first-episode schizophrenia treatment programs. Results also indicate that community rather than university control groups represent more valid comparison groups in first-episode schizophrenia research.

A 60-year-old Man with Major Depression

&lt;P&gt;This 60-year-old man was referred by his psychotherapist whom he had been seeing twice a week for 12 years. He was in his fourth episode of non-psychotic major depression. He had no history of mania or hypomania. His first episode began at age 43. Each episode had an acute onset, reaching the nadir within 2 months of onset. He had full recovery between each episode. He was symptom-free in these inter-episode periods, during which function was normal. Each successive episode was longer and more severe than the prior one. It was difficult to pinpoint stressors that precluded the onset of each episode.&lt;/P&gt; &lt;H4&gt;ABOUT THE AUTHOR&lt;/H4&gt;&lt;P&gt;A. John Rush, MD, is Vice Chair, Department of Clinical Sciences, and Professor, Department of Psychiatry, Betty Jo Hay Distinguished Chair in Mental Health, Rosewood Corporation Chair in Biomedical Science, University of Texas Southwestern Medical Center, Dallas, Texas.&lt;/P&gt;&lt;P&gt;Dr. Rush disclosed the following relevant financial relationships: Advanced Neuromodulation Systems, AstraZeneca; Best Practice Project Management, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Forest Pharmaceuticals, Gerson Lehman Group, GlaxoSmithKline, Jazz Pharmaceuticals, Magellan Health Services, Merck, Neuronetics, Ono Pharmaceuticals, Organon Pharmaceuticals, Pamlab, Personality Disorder Research Crop., Pfizer, Urban Institute, and Wyeth: Consultant; Cyberonics, Forest Pharmaceuticals, and GlaxoSmithKline: Member of Speakers’ Bureau; National Institute of Mental Health, Robert Wood Johnson Foundation, and Stanley Medical Research Institute: Research Support; Guilford Publications and Healthcare Technology Systems: Royalties; and Pfizer: Stockholder.&lt;/P&gt;

Keeping Our Depressed Patients in the Right Treatment Long Enough for Them to Get Better: Some Hopeful Findings

Keeping Our Depressed Patients in the Right Treatment Long Enough for Them to Get Better: Some Hopeful Findings

Neuropsychological performance in partly remitted unipolar depressive patients: focus on executive functioning

Only few studies have investigated executive impairment in the euthymic phase of unipolar affective disorders, yielding diverging results. The role of impulsivity/orbitofrontal associated executive functioning in remitted depression has not yet been examined. Partly remitted male out-patients (n = 15) with non-psychotic major depression (MDD) were compared with healthy males (n = 15) on several neuropsychological tests. Executive tasks focussed on orbitofrontal function (Go/No-Go, Iowa Gambling Task (IGT), delayed alternation task). Furthermore, the Barratt Impulsiveness Scale (BIS-11) was administered to all subjects. Executive skills of the patients were largely unimpaired. Patients exhibited significant deficits on measures of verbal memory only. Residual depressive symptoms in patients were correlated with diminished response inhibition. BIS-11 scores were not elevated in the patients. Both executive impairment related to orbitofrontal function and self-reported impulsive behaviour in major depression seem to be state-dependent. In accordance with other studies, patients with remitted unipolar depression showed a persistent verbal memory loss.

Dysfunctional cognitions in hospitalized patients with psychotic versus nonpsychotic major depression

Previous research suggests that psychotic major depression (PMD) is associated with greater illness severity and functional impairment as well as poorer treatment response to antidepressants and psychotherapies compared with nonpsychotic major depression. Although patients with PMD exhibit a number of neurobiological abnormalities, little research has been conducted to date on possible psychological factors that are related to illness in this depression subtype. In the current study, baseline data were pooled from 2 clinical trials in which depressed patients (n = 235) were recruited during a psychiatric hospitalization for an acute episode. Twelve percent (n = 28) of this treatment-seeking sample met criteria for PMD and showed elevated levels of depression severity and dysfunctional beliefs compared with individuals with nonpsychotic major depression. However, even after controlling for depression severity and other relevant baseline variables, only a measure of common dysfunctional beliefs differentiated those with vs those without psychotic features. Furthermore, higher levels of depressive cognitions were related to poorer psychosocial functioning and suicidality in PMD patients. Results suggest that elevated levels of common negative cognitions in depressed patients may be associated with the presence of more severe psychotic symptoms. Adapted cognitive-behavioral treatments may be useful for treating patients with PMD specifically.

Trends in the Use of Psychotropic Drugs in Taiwan: A Population-Based National Health Insurance Study, 1997-2004

Trends in the Use of Psychotropic Drugs in Taiwan: A Population-Based National Health Insurance Study, 1997-2004

Out-patient care to schizophrenic patients having antisocial records

Background: Depression occurring in schizophrenia is a common problem; however, investigators have typically not studied it with the paranoid/nonparanoid dichotomy in mind. This study examines the quality as well as the severity of depression in three psychiatric groups: paranoid schizophrenia patients, nonparanoid schizophrenia patients, and nonpsychotic major depression patients. Method: Clinical and sociodemographic data were collected on 27 paranoid and 27 nonparanoid schizophrenia patients during their postpsychotic phase while they were at least mildly depressed, and a comparison group of 27 nonpsychotic patients diagnosed with major depressive disorder. The three groups were then assessed on various psychometric scales for severity of depression, profile of symptoms, suicidal risk, and anhedonia. Results: The paranoid schizophrenia patients were more depressed and more at risk for suicide than the nonparanoid schizophrenia patients, yet their depressive profiles and levels of anhedonia were similar. Conclusions: Depressed mood and anhedonia constitute serious problems for schizophrenia patients, but particularly for paranoid schizophrenia patients during the postpsychotic phase of their illnesses. Clinical implications: Schizophrenia patients, especially those with the paranoid features, should be routinely evaluated and monitored for depression. Apart from treatment with drugs, cognitive therapy may be considered a viable option, particularly for paranoid schizophrenia patients. Limitations: Gender was not matched for the two schizophrenia groups and extrapyramidal side effects were not measured.

Placebo Response and Antidepressant Response

Much of the response to an antidepressant is the result of placebo response. The placebo response embedded in drug response confounds studies seeking to identify brain mechanisms essential for pharmacologic response. Exclusion of patients who fail to meet entry criteria at the end of a placebo lead-in phase has been inadequate to reduce the effect of placebo during pharmacologic trials. This study focused on the placebo lead-in phase and examines whether change in severity of depression during placebo lead-in predicts change in depressive symptoms during antidepressant treatment. The subjects were patients aged 60-85 years with nonpsychotic unipolar major depression not attributed to dementing disorders, medical illnesses, or drugs causing depression and had a 24-item Hamilton Depression Rating Scale score of 18 or greater. After a two-week placebo lead-in, subjects with Hamilton Depression Rating Scale score of 18 or greater received 10 mg escitalopram for 12 weeks. Worsening or limited change in depression during placebo treatment predicted improvement in depressive symptoms during escitalopram treatment. Limited change in anxiety, melancholia, helplessness, and paranoia during placebo treatment were the strongest predictors of improvement in depression while on escitalopram. These findings, if replicated, may be used to characterize depressed older patients likely to respond to the pharmacologic action of antidepressants rather than the placebo response embedded in drug trials and thus improve the methodology of biomarker studies of antidepressant response. On a clinical level, depressed older patients who improve during a prolonged evaluation may be candidates for nonpharmacologic treatments because their drug response may be limited.