Chronic mood disorders in depressed outpatients: Diagnosis and response to pharmacotherapy

The current study was devised to assess the utility of Research Diagnostic Criteria (RDC) categories used to classify minor mood disorders. Similar categories are to be used in the APA's Diagnostic and Statistical Manual, 3rd edition. The patient sample consisted of 64 consecutive admissions to a double-blind trial of amitriptyline, perphenazine and the combination as treatment for depression. Patients who met RDC for a current episode of major depressive disorder were given 4 weeks of pharmacotherapy as treatment.Chronic mood disorders were also assessed using RDC criteria. This evaluation revealed that only 34% met criteria for an episode of major depressive disorder alone, while 36% met criteria for intermittent depressive disorder, 14% for cyclothymic personality and 16% for labile personality in addition to being in a current major depressive episode. These 4 diagnostic subgroups were compared on demographic characteristics, childhood history, psychiatric history, presenting patterns of symptoms and social functioning, and response to treatment. Differences were noted in the subgroups in presenting symptom levels and residual impairment. However, there was no differential response to a brief course of antidepressant pharmacotherapy in patients with and without chronic minor mood disorders. Most patients showed an improvement during the brief course of treatment. Thus, the presence of a chronic minor mood disorder does not appear to be a contraindication for use of medication in patients who also are currently experiencing a major depressive episode.     

Training primary care physicians in Chile in the diagnosis and treatment of depression

OBJECTIVES: This study evaluated the results of a brief 2-day educational training program for Chilean primary care physicians that measured changes in knowledge, attitudes and practice. This World Psychiatric Association (WPA) program was adopted to overcome diagnostic and treatment problems that are found among primary care practitioners. METHODS: 37 primary care physicians from two cities in Chile and 2589 patients participated. Physician's knowledge, attitudes and clinical practice were assessed 1 month prior and 1 month following the training program. In addition, the patients that visited the clinic during a typical week completed depression symptom self-ratings, including the Zung and a DSM-IV/ICD-10 major depression checklist at both times. RESULTS: The results suggested that, with this group of Chilean doctors, the WPA program was effective in improving knowledge about depression and in changing some disorder-related attitudes. In addition, it had some limited impact on actual clinical practice, although the rate of diagnosis remained stable and the post-training agreement between physician diagnosis and patient self-report remained low. The physicians seemed more confident in treating patients and demonstrated increased use of antidepressant agents. CONCLUSION: The inclusion of primary care physicians is a central component of any initiative to reduce the treatment gap and lag of depression, but their competence to play a crucial role remains limited. Further training of primary care physicians to improve the management of major depression continues to be needed.     

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

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

Dropouts versus completers among chronically depressed outpatients

BACKGROUND: Premature termination is common among patients treated for depression with either pharmacotherapy or psychotherapy. Yet little is known about factors associated with premature treatment termination among depressed patients. METHODS: This study examines predictors of, time to, and reasons for dropout from the 12-week acute phase treatment of nonpsychotic adult outpatients, age 18-75, with chronic major depression who were randomly assigned to nefazadone alone (MED), cognitive behavioral analysis system of psychotherapy alone (CBASP) or both treatments (COMB). RESULTS: Of 681 randomized study participants, 156 were defined as dropouts. Dropout rates were equivalent across the three treatments. Among dropouts, those in COMB remained in treatment (Mean=40 days) significantly longer than those in either MED (Mean=27 days) or CBASP (Mean=28 days). Dropouts attributed to medication side-effects were significantly lower in COMB than in MED, suggesting that the relationship with the psychotherapist may increase patient willingness to tolerate side-effects associated with antidepressant medications. Ethnic or racial minority status, younger age, lower income, and co-morbid anxiety disorders significantly predicted dropout in the full sample. Within treatments, differences between completers and dropouts in minority status and the prevalence of anxiety disorders were most pronounced in MED. Among those receiving CBASP, dropouts had significantly lower therapeutic alliance scores than completers. LIMITATIONS: The sample included only individuals with chronic depression. CONCLUSIONS: Predictors of dropout included baseline patient characteristics, but not early response to treatment. Ethnic and racial minorities and those with comorbid anxiety are at higher risk of premature termination, particularly in pharmacotherapy, and may require modified treatment strategies.     

Residual symptoms and recurrence during maintenance treatment of late-life depression

BACKGROUND: Many older patients who recover from an episode of major depression continue to suffer from depressed mood, anxiety, and sleep problems. Our study assesses the impact of these residual symptoms on the risk of recurrence during maintenance treatment of late-life depression. METHOD: We analyzed data from a randomized clinical trial of maintenance treatment in patients with unipolar depression aged > or =70, 116 of whom remitted and remained stable during open pharmacotherapy and interpersonal psychotherapy (IPT) and were randomized to clinical management/pharmacotherapy; clinical management/placebo; monthly maintenance IPT/ pharmacotherapy; or monthly maintenance IPT/placebo. We assessed the impact of overall residual symptoms (based on the Hamilton Depression Rating Scale (HAM-D) total score) and of specific residual symptom clusters - mood symptoms (depressed mood, guilt, suicidality, energy/interests), sleep disturbance (early, middle, late insomnia), and anxiety (agitation, psychic and somatic anxiety, hypochondriasis) measured at randomization. Sleep disturbance was also assessed with the Pittsburgh Sleep Quality Index (PSQI). We used Cox proportional hazards regression models controlling for assignment to antidepressant medication versus placebo to identify predictors of recurrence. RESULTS: Residual anxiety and residual sleep disturbance (as measured by the PSQI but not the HAM-D) independently predicted early recurrence. LIMITATIONS: Use of HAM-D clusters to define residual symptoms; analysis limited to completers of acute and continuation treatment. CONCLUSIONS: In patients with late-life depression who have remitted with pharmacotherapy and psychotherapy, the deleterious effect of residual symptoms is due to persisting anxiety and, possibly, residual sleep disturbance.     

Attitudes to depression and its treatment in primary care

BACKGROUND: Undertreatment of depression in primary care is common. Efforts to address this tend to overlook the role of patient attitudes. Our aim was to validate and describe responses to a questionnaire about attitudes to depression and its treatment in a sample with experience of moderate and severe depressive episodes. METHOD: Cross-sectional survey of 866 individuals with a confirmed history of an ICD-10 depressive episode in the 12 months preceding interview, recruited from 7271 consecutive general practitioner (GP) attendees in 36 general practices in England and Wales. Attitudes to and beliefs about depression were assessed using a 19-item self-report questionnaire. RESULTS: Factor analysis resulted in a three-factor solution: factor 1, depression as a disabling, permanent state; factor 2, depression as a medical condition responsive to support; and factor 3, antidepressants are addictive and ineffective. Participants who received and adhered to antidepressant medication and disclosed their depression to family and friends had significantly lower scores on factors 1 and 3 but higher scores on factor 2. CONCLUSIONS: People with moderate or severe depressive episodes have subtle and divergent views about this condition, its outcome, and appropriate help. Such beliefs should be considered in primary care as they may significantly impact on help seeking and adherence to treatment.     

Do characteristics of patients with major depressive disorder differ between primary and psychiatric care?

BACKGROUND: Despite the need for rational allocation of resources and cooperation between different treatment settings, clinical differences in patients with major depressive disorder (MDD) between primary and psychiatric care remain obscure. We investigated these differences in representative patient populations from primary care versus secondary level psychiatric care in the city of Vantaa, Finland. METHOD: We compared MDD patients from primary care in the Vantaa Primary Care Depression Study (PC-VDS) (n=79) with psychiatric out-patients (n=223) and in-patients (n=46) in the Vantaa Depression Study (VDS). DSM-IV diagnoses were assigned by the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I in PC-VDS) or Schedules for Clinical Assessment in Neuropsychiatry (SCAN in VDS), and SCID-II interviews. Comparable information was collected on depression severity, Axis I and II co-morbidity, suicidal behaviour, preceding clinical course, and attitudes towards and pathways to treatment. RESULTS: Prevalence of psychotic subtype and severity of depression were highest among in-patients, but otherwise few clinical differences between psychiatric and primary care patients were detected. Suicide attempts, alcohol dependence, and cluster A personality disorder were associated with treatment in psychiatric care, whereas cluster B personality disorder was associated with primary care treatment. Patients' choice of the initial point of contact for current depressive symptoms seemed to be independent of prior clinical history or attitude towards treatment. CONCLUSIONS: Severe, suicidal and psychotic depression cluster in psychiatric in-patient settings, as expected. However, MDD patients in primary care or psychiatric out-patient settings may not differ markedly in their clinical characteristics. This apparent blurring of boundaries between treatment settings calls for enhanced cooperation between settings, and clearer and more structured division of labour.     

The significance of secondary depression

Secondary depression is a depression in an individual who has one or more preexisting, nonaffective psychiatric disorders or an incapacitating or life-threatening medical illness which precedes and parallels the symptoms of depression. Secondary depression is commonly seen in patients presenting to psychiatric facilities. For every 5 patients who are seen with a diagnosis of depression, approximately 2 should be classified as secondary. A patient with secondary depression is more likely to be younger, male, and to have a family history of alcoholism. His first diagnosis is most likely to be alcoholism; however, the preceding diagnosis varies depending on the setting in which the patient is seen. Hysteria, sociopathy, drug abuse and anxiety neurosis are also common. The symptom picture of secondary depression is almost indistinguishable from primary depression. One important reason a patient enters psychiatric treatment is that he develops a coexistent depression.     

A randomised,double-blind comparison of milnacipran and imipramine in the treatment of depression

This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for milnacipran. The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, milnacipran constitutes an important new treatment option in major depression.     

Dexamethasone suppression test in masked depression

The dexamethasone suppression test (DST), family history, response to antidepressant medication and short-term course were investigated in 16 female patients with masked depression. Twelve patients showed abnormal DST results, 3 patients had positive family history of affective illness in first-degree relatives, 11 responded well to antidepressant drug treatment and 3 showed definite hypomanic episodes during follow-up. The results suggest that masked depression is a special form of primary (endogenous) depressive illness, and that the DST is a good diagnostic aid not only in the 'classical' but also in masked forms of depressive disorders.     

The acceptability of a culturally-tailored depression education videotape to African Americans

The aim of this project was to determine the acceptability and usefulness of an educational videotape for African Americans with depression. Four focus groups were held in two community settings and at a historically black university. Subjects included 24 African Americans, aged 18-76 years, who screened positive for depression. Focus group questions addressed the usefulness of the videotape to understand depression and its treatment, the most and least effective parts of the videotape, and the cultural appropriateness of the information presented. Participants took pre- and post-tests on attitudes about depression. Discussions were audiotaped, transcribed, and reviewed independently by two investigators to identify and group comments into specific themes. Two other investigators reviewed the themes and comments for consistency and relevance. The videotape was generally well received and was rated effective in improving knowledge about depression and its treatment. After watching the videotape, attitudes improved in several areas, including depression as a medical illness, effectiveness of treatment, negative perceptions of antidepressant medication and reliance upon spirituality to heal depression. This culturally tailored videotape about depression is deemed acceptable and effective for most African Americans with depression participating in focus groups. It also improved knowledge and several attitudes about depression.     

Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder.

BACKGROUND: Borderline personality disorder (BPD) has long defined definitive treatment. Such failure is reflected in repeated suicidal crises, often associated with dysphoric symptoms of a chronic fluctuating nature, whose labile intermittent character does suggest a subthreshold bipolar depressive mixed state. For all these reasons, we hypothesized that the anticonvulsant lamotrigine, touted to be a mood stabilizer with antidepressant properties, might be uniquely beneficial for these patients. METHODS: From a base rate of about 300 patients in a community mental health center, we identified eight patients meeting seven or more of the DSM-IV criteria for BPD without concurrent major mood disorders. All patients presented with history of severe suicidal behavior, hostile depression and/or labile moods, stimulant and alcohol abuse, as well as multiple unprotected sexual encounters; one patient was actually HIV positive. All had failed previous trials with different antidepressants and mood stabilizers. All current medications were gradually withdrawn--and when necessary--patients kept on a low dose of a conventional neuroleptics for a few weeks, while lamotrigine was being gradually introduced in 25-mg weekly increments until the patient responded (up to 300 mg/day maximum). RESULTS: Consistent with previous work by us and others, bipolar family history could be documented in three of eight BPD patients, and worsening on antidepressants in four of eight, providing indirect support to our conceptualization of BPD as a bipolar variant. One patient developed a rash on 25 mg and was dropped from the lamotrigine trial, while another patient was noncompliant. Three who failed lamotrigine, subsequently responded, respectively, to sertraline, lithium-thioridazine combination, and valproate. The remaining three patients showed a robust response to lamotrigine, ranging from 75 to 300 mg/day: their functioning jumped from a mean baseline DSM-IV GAF score in the 40's to the 80's during 3-4 months. Among all responders impulsive sexual, drug-taking and suicidal behaviors disappeared and no longer met the criteria for BPD. At an average follow-up of 1 year, they no longer meet criteria for BPD. LIMITATIONS: Open uncontrolled results on a small number of patients in a tertiary care center may not generalize to BPD patients at large. CONCLUSIONS: Overall, the BPD response to pharmacotherapy in the present case series was 75%. The fact that five of six pharmacotherapy responders required mood stabilizers, argues against the prevalent view that the depressions of borderline patients belong to unipolarity. Of BPD patients who completed the trial, 50% achieved sustained remission from their personality disorder with lamotrigine monotherapy. The dramatic nature of the response in patients refractory to all previous medication trials and maintenance of a robust response over 1 year, argue against a placebo effect. Controlled systematic investigation of lamotrigine in BPD is indicated.     

The implications of DSM-III personality disorders for patients with major depression

We studied 78 inpatients with DSM-III major depression. Forty-one (53%) had a concurrent personality disorder (PD) according to a detailed structured interview for DSM-III personality disorders. The patients with depression plus PD differed from patients with depression alone on numerous measures. The PD patients had earlier onset; higher HRS scores; poorer social support; more life stressors; more frequent separation and divorce; more frequent nonserious suicide attempts, less frequent dexamethasone nonsuppression; poorer response to antidepressant medication; and higher risk for depression, alcoholism and antisocial personality among first-degree relatives. The PD subgroup shares many attributes with Winokur's subtype of depression spectrum disorder and Akiskal's character spectrum disorder. An attempt to identify a subgroup of personality disorders which might be an atypical affective disorder was inconclusive. However, patients in DSM-III cluster III were similar to the patients with no-PD on the dexamethasone suppression test, response to treatment, and familial risk for depression and antisocial personality.     

Mental Health Treatment Preferences of Primary Care Patients

Primary care patients were surveyed about emotional symptoms, treatment history, and treatment preferences. Four hundred and one patients completed questionnaires while waiting for appointments, and 271 (68%) mailed back additional materials. Many patients expressed a desire for help with the way they were feeling; understanding the cause of one's feelings was most commonly identified as likely to be helpful. Most preferred individual intervention. A range of attitudes and pragmatic concerns were barriers to seeking care. More patients said that they would likely to attend a fitness program than counseling, stress management, or healthy living classes. Distressed patients were more likely to say that they would seek medications and less likely to feel that they weren't the type to seek care or that they could work it out themselves. This work supports the need for continued patient education and for primary care-based mental health services that are responsive to patients' preferences.     

Sexual dysfunction before antidepressant therapy in major depression

BACKGROUND: Decreased sexual interest and function both occur as a consequence of antidepressant medication use, and are especially associated with serotonin reuptake inhibitors (SRIs). However, few investigators have reported the base rate for disturbances in sexual desire, arousal and orgasm or ejaculation in patients with major depression (MD) prior to antidepressant treatment. The purpose of this report is to define the frequency of sexual dysfunction (SD) in 134 patients with MD and examine the relationship between SD and demographic, clinical and personality variables. METHOD: A consecutive series of 55 male and 79 female MD patients diagnosed by SCID-DSM IV assessment completed a series of psychometric measures including a Sexual Function Questionnaire, which asked about change in sexual interest and function as well as sexual activity during the preceding month. RESULTS: Only 50% of women and 75% of men reported sexual activity during the preceding month. Over 40% of men and 50% of women reported decreased sexual interest. Reduced levels of arousal were more common in both men and women (40-50%) than ejaculatory or orgasm difficulties (15-20%). In women, problems with arousal and orgasm correlated with higher neuroticism and lower extraversion. There was no relationship between SD and personality measures in men. While age at onset of depression and number of prior episodes showed a modest correlation with SD measures, there were no correlations with severity of depression or specific symptoms clusters. LIMITATIONS AND CONCLUSIONS: Although limited by a relatively small sample of drug free patients with MD, and by the absence of a non-depressed comparison sample, these results emphasize the importance of factors beyond specific drug effects in the assessment of antidepressant related sexual dysfunction.     

Clinical effects of abrupt withdrawal from tri-cyclic antidepressants and monoamine oxidase inhibitors after long-term treatment

51 psychiatric outpatients with depressive, anxiety and phobic neuroses were withdrawn from their maintenance treatment with tricyclic antidepressant drugs or the monoamine oxidase inhibitor, phenelzine, at a time mutually agreed between patient and doctor. Self-ratings of anxiety and depression were recorded at the time of withdrawal and at weekly intervals thereafter for 4 weeks. An increase in symptoms after withdrawal was found to be more likely after longer duration of maintenance treatment and in patients taking phenelzine.     

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

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

Suicidal behaviour among primary-care patients with depressive disorders

BACKGROUND: Most national suicide prevention strategies set improved detection and management of depression in primary health care into a central position. However, suicidal behaviour among primary-care patients with depressive disorders has been seldom investigated. METHOD: In the Vantaa Primary Care Depression Study, a total of 1119 primary-care patients in the City of Vantaa, Finland, aged 20 to 69 years, were screened for depression with the Primary Care Evaluation of Mental Disorders (PRIME-MD) questionnaire. Depressive disorders were diagnosed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and the 137 patients with depressive disorder were included in the study. Suicidal behaviour was investigated cross-sectionally and retrospectively in three time-frames: current, current depressive episode, and lifetime. Current suicidal ideation was measured with the Scale for Suicidal Ideation (SSI), and previous ideation and suicide attempts were evaluated based on interviews plus medical and psychiatric records. RESULTS: Within their lifetimes, 37% (51/137) of the patients had seriously considered suicide and 17% (23/137) attempted it. Lifetime suicidal behaviour was independently and strongly predicted by psychiatric treatment history and co-morbid personality disorder, and suicidal behaviour within the current episode was predicted most effectively by severity of depression. CONCLUSIONS: Based on these findings and their convergence with studies of completed suicides, prevention of suicidal behaviour in primary care should probably focus more on high-risk subgroups of depressed patients, including those with moderate to severe major depressive disorder, personality disorder or a history of psychiatric care. Recognition of suicidal behaviour should be improved. The complex psychopathology of these patients in primary care needs to be considered in targeting preventive efforts.     

Is gender a factor in psychiatrists' evaluation and treatment of patients with major depression?

BACKGROUND: Gender differences in clinical assessment and treatment have been reported in several areas of medicine. We examine whether differences exist in the routine outpatient psychiatric management of men and women with major depression. METHODS: Psychiatrists practicing in the community completed case forms on a systematic sample of their adult outpatients with major depression. Comparisons are presented between male (n=261) and female (n=472) patients focusing on their background characteristics, clinical presentation, assessment, and treatment. Significant gender disparities in assessment and treatment are also examined with respect to the gender of the treating psychiatrist. RESULTS: Although male and female patients had generally similar clinical profiles, a significantly greater proportion of males than females had psychomotor retardation and substance use disorders. No significant gender differences were observed in the assessment of depressive symptoms, psychiatric comorbidities, and treatment with antidepressant medications or psychotherapy. However, a significantly smaller percentage of depressed women than men received assessments of sexual function and medication-related sexual side effects. Female patients were also less likely to have discussed their treatment preferences with their psychiatrists. LIMITATIONS: Only a minority (33.2%) of psychiatrists invited to participate contributed patients to this study. The results are based on structured assessments completed by practicing psychiatrists rather than patient self-assessments or independent research assessments. CONCLUSIONS: Although we find overall little evidence of gender bias in the clinical management of major depression, both male and female psychiatrists need to further explore sexual function and treatment preferences in female patients.     

Comparison of the family history method to direct interview: Factors affecting the diagnosis of depression

This study compares information on the diagnosis of depression obtained by family history reports with the information obtained by direct interview. Reports were obtained from family memebers on the psychiatric status of 696 individuals for whom direct SADS-L interviews were also available. The effects on family history reports of subjects characteristics, treatment status, age of onset of depression, and endogenous symptoms were examined. Sensitivity and specificity for family history reports on the specific symptoms of depression are also reported. The specificity of family history reports for the diagnosis of depression was consistently high but sensitivity varied as a function of subject and illness characteristics. Sensitivity was somewhat higher for females than males and appreciably higher for probands than for their first-degree relatives and spouses. Sensitivity was increased whenever treatment, hospitalization or endogenous symptoms were present in the subject, indicating that family history reports are most accurate for detecting the cases of depression. Finally, the symptoms of depression that are least accurately reported by relatives are identified and suggestions for modifying the family history criteria for depression are proposed.