The association between moderate alcohol use and illness severity in bipolar disorder: a preliminary report

OBJECTIVE: To examine the association of alcohol consumption with symptoms, illness course, and health care utilization among non-alcoholic patients with bipolar disorder. METHOD: Subjects were 148 patients with bipolar I or II disorder enrolled in a longitudinal study of cognitive-behavioral therapy versus psychoeducation. Subjects were 18 to 60 years old, in full or partial remission, and non-heavy drinkers with no history of substance use disorders. At least 4 weeks of consistent naturalistic treatment with mood stabilizer was required for enrollment. Measures included the Structured Clinical Interview for DSM-IV, the Hamilton Rating Scale for Depression, the Clinician-Administered Rating Scale for Mania, and the Khavari Alcohol Test. Data were gathered from July 2002 to December 2004. RESULTS: Mean weekly alcoholic beverage consumption was minimal among both men (3.8 standard drinks, SD = 8.9) and women (1.2 standard drinks, SD = 1.9). Nonetheless, total alcohol consumption among men was associated with lifetime manic episodes (F = 10.2, df = 1, p = .003) and emergency department visits (F = 4.3, df = 1, p = .046). Spirits consumption among men was strongly associated with lifetime manic episodes (F = 81.8, df = 1, p < .001) and emergency department visits (F = 14.0, df = 1, p < .001). Among women, the frequency of alcohol consumption was associated with lifetime episodes of depression (F = 15.5, df = 1, p < .001) and hypomania (F = 4.8, df = 1, p < .03). Wine consumption among women was associated with lifetime hypomanic episodes (F = 13.6, df = 1, p < .001) and current manic symptoms (F = 4.0, df = 1, p < .05). CONCLUSION: Despite low volumes of consumption, alcohol was associated with measures of illness severity in bipolar disorder among both men and women. The adverse effects of alcohol on bipolar disorder may occur over a range of consumption, rather than being confined to heavy drinkers.     

Gender Differences in Response to CBT-Orientated Multimodal Treatment in Depressed Patients with Chronic Pain

Objective: Although gender differences are increasingly the focus of current research, gender aspects in the response to pharmacological and non-pharmacological treatment of depression still remain unclear. The aim of this study was to analyze the impact of gender on the outcome of a CBT-orientated multimodal treatment in depressed outpatients with chronic pain.Methods: A total of 298 patients (154 women) underwent a standardized five-week CBT-orientated multimodal treatment. Depressive symptoms were measured at the beginning and end of the treatment with the German version of the Center for Epidemiological Studies Depression Scale (CES-D).Results: The improvement of depressive symptoms showed an effect size (ES) of 0.81 in the total sample. However, women improved considerably more (ES 0.96) than did men (ES 0.65) and these gender differences are seen in the complete sample (t = 2.757, df = 296, p = 0.006) as well as in the group without received antidepressants (t = 2.325, df = 151, p = 0.021).Conclusion: Women with a depressive disorder and chronic pain benefit significantly more from a CBT-orientated multimodal treatment and exhibit a considerably greater reduction of depressive symptoms than do men. These distinctions are not due to differences in received antidepressant medication, psychiatric comorbidities or educational background.     

Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: a positron emission tomography study with fluorine-18-labeled setoperone.

BACKGROUND: The neuroreceptor changes involved in therapeutic efficacy of various antidepressants remain unclear. Preclinical studies have shown that long-term administration of various antidepressants causes down-regulation of brain serotonin 2 (5-HT2) receptors in rodents, but it is unknown if similar changes occur following antidepressant treatment in depressed patients. Our purpose, therefore, was to assess the effects of treatment with desipramine hydrochloride on brain 5-HT2 receptors in depressed patients using positron emission tomography (PET) and fluorine-18 (18F)-labeled setoperone. METHODS: Eleven patients who met DSM-IV criteria for major depression as determined by a structured clinical interview for DSM-III-R diagnosis and suitable for treatment with desipramine were recruited. Ten patients underwent a PET scan before and another after 3 to 4 weeks of treatment with desipramine. RESULTS: Eight of the 10 patients responded to desipramine treatment as indicated by more than 50% decrease in Hamilton Depression Rating Scale scores. Depressed patients showed a significant decrease in 5-HT2 receptor binding as measured by setoperone binding in frontal, temporal, parietal, and occipital cortical regions following desipramine treatment. The decrease in 5-HT2 receptor binding was observed bilaterally and was particularly prominent in frontal cortex. CONCLUSIONS: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is unknown if this change in 5-HT2 receptors is due to clinical improvement or an effect of desipramine that is unrelated to clinical status.     

Efficacy of desipramine in depressed outpatients. Response according to research diagnosis criteria diagnoses and severity of illness

The efficacy of desipramine for mild depression was tested in a double-blind, placebo-controlled study of outpatients with scores below 19 on the Hamilton Rating Scale for Depression (HAM-D). Of 103 such patients, 23 dropped out and 16 improved during a ten-day placebo period. Among 64 patients completing the randomized portion of the study, significantly more improved with desipramine that with placebo. The Research Diagnostic Criteria (RDC) category of major depressive disorder largely accounted for the drug-placebo response difference found for the entire sample. Patients with intermittent depressive disorder improved significantly less frequently with desipramine than patients with major depressive disorder. Independent of RDC diagnosis, severity of illness correlated with outcome. Thus, patients with pretreatment HAM-D scores at or above the median demonstrated significant drug effect, while patients with lower pretreatment HAM-D scores did not.     

Recognition and treatment of depression in Parkinson's disease

Depression in Parkinson's disease (PD) is common, but little is known about its recognition and treatment. The authors report the antidepressant experience (N = 100) and outcome of depression assessment (n = 77) of a convenience sample of patients at a PD center. Subjects were assessed with a psychiatric and neurological battery, and information was gathered on depression treatment. One third (34%) of subjects met criteria for a depressive disorder, and two thirds (65%) of them were not currently receiving antidepressant treatment. Approximately one quarter (23%) of subjects were taking an antidepressant, but almost half (47%) of them still met criteria for a depressive disorder. Few antidepressant users with persistent depression had received either antidepressant treatment at dosages within the highest recommended range (11%) or more than 1 antidepressant trial (33%). Most depressed patients are untreated, and half of antidepressant users remain depressed, suggesting that even when delivered, treatment is often inadequate or ineffective.     

Do depressed subjects who have failed both fluoxetine and a tricyclic antidepressant respond to the combination?

BACKGROUND: Recent evidence suggests that the combination of fluoxetine and desipramine may provide a rapid and effective treatment for depression. METHOD: The current study evaluated 13 subjects with DSM-III-R nonpsychotic major depression who had previously failed either desipramine or imipramine and who were currently unsuccessfully treated with fluoxetine. Desipramine or imipramine was added to fluoxetine and Hamilton Rating Scale for Depression (HAM-D) scores, Beck Depression Inventory (BDI) scores, and plasma tricyclic levels were monitored for 3 weeks. RESULTS: Of the 13 subjects, 7 (54%) had a greater than 40% decline in HAM-D scores and 4 of these (31%) had 50% or greater decline in HAM-D. At week 3, responders (767 +/- 282 nmol/L) had a significantly higher mean tricyclic level as compared with nonresponders (515 +/- 95 nmol/L, F = 25.1, p < .0001), and change in BDI scores was significantly correlated with tricyclic level (r = -0.60, p < .05). CONCLUSION: These findings suggest that in some subjects the positive clinical effect of combining fluoxetine and a tricyclic antidepressant may be related to the plasma levels of the tricyclic compound.     

The effect of antidepressant treatment on N-acetyl aspartate levels of medial frontal cortex in drug-free depressed patients

The medial frontal cortex has been shown to modulate emotional behavior and stress responses, suggesting that the dysfunction of this region may be involved in the pathogenesis of depressive symptoms. The present study was performed to determine whether there was any effect of antidepressant treatment on the metabolite levels in the left medial frontal cortex as measured by proton magnetic resonance spectroscopy in depressed patients. Twenty patients diagnosed as having major depressive disorder according to DSM-IV and 18 healthy volunteer subjects were included in the study. Twelve of patients had their first episode and were drug-na?ve. Other depressed patients were drug-free for at least 4 weeks. The severity of depression was assessed by HAM-D and Clinical Global Impression Scale-Severity (CGI-S). Single voxel, 8 cm(3), 1H MR spectra of left medial frontal cortex was acquired both before and following antidepressant treatment. The concentrations and ratios of N-acetyl aspartate (NAA), Creatine+Phosphocreatine (Cr+PCr) and Choline (Cho) were measured. Pretreatment NAA/Cr values of patients were lower than those of healthy controls, but this difference did not reach to statistically significant levels (t=1.83, df=36, p=0.07). However, antidepressant treatment had significant effect on NAA/Cr ratios (groupxtreatment interaction: F=9.93 df=1,36, p=0.03). After the treatment, NAA/Cr values of patients increased significantly compared to pretreatment values (t=3.32, df=19, p=0.004). No significant difference was observed between the post-treatment NAA/Cr values of patients and those of controls (t=1.64, df=36, p=0.19). Correlation analysis detected negative correlation between pretreatment CGI-S scores and NAA/Cr ratios (r=-0.51, p=0.02). This preliminary result suggests that there might be a possible defect in the neuronal integrity in the left medial frontal cortex (mainly left anterior cingulate cortex) of depressed patients. Antidepressant treatment with its neurotrophic effects might play a positive role in restoring the neuronal integrity. Further studies are needed to support these initial findings.     

Integrated treatment of comorbid depression and substance use disorders.

OBJECTIVE: The goals of this 6-month prospective study were to evaluate the effect of a current diagnosis of depression on the course and outcome of addiction treatment and to determine whether patients with depression received or required additional treatment compared with those without depression. METHOD: On entering addiction treatment, 75 men and 45 women with substance use disorders were assessed by clinical and semistructured interviews, Global Assessment Scale, Hamilton Rating Scale for Depression, Beck Depression Inventory, and revised 90-item Symptom Checklist. RESULTS: Forty-three patients (35.8%) met DSM-IV criteria for a current depressive disorder at intake into addiction treatment. The depressed patients had significantly (p < .0001) higher levels of psychopathology at intake. However, contrary to previous studies, they fared as well as the nondepressed patients in terms of all addiction outcome measures and all indicators of psychiatric status at 6 months. During the 6-month follow-up period, the depressed patients received more treatment than the nondepressed patients. Specifically, they had more psychiatric appointments, and they were more likely to require inpatient detoxification and to be prescribed new antidepressant medication regimens. CONCLUSION: Depression comorbidity may not have had a negative impact on the course and outcome of addiction treatment because the dual disorder was identified at the initial assessment, and integrated psychiatric care was available. It may be that additional treatment compensated for greater psychopathology among dual-disorder patients.     

A 20-year longitudinal observational study of somatic antidepressant treatment effectiveness

OBJECTIVE: This observational study examined the effectiveness of somatic antidepressant treatments as administered in the community. METHOD: The study group consisted of 285 subjects with an intake diagnosis of major depressive disorder who had entered the National Institute of Mental Health Collaborative Depression Study as early as 1978, had at least one additional affective episode, and had been followed for up to 20 years, as recently as 1999. The characteristics that distinguished subjects receiving various levels of somatic antidepressant treatment were accounted for in what was called a propensity for treatment intensity model. The effectiveness of somatic antidepressant treatment during major affective episodes was then examined. RESULTS: Those who received higher levels of antidepressant treatment tended to have more prior episodes, more severe depressive symptoms, and more intensive somatic therapy during prior episodes and prior well intervals than those who received lower levels. Treatment effectiveness analyses that were stratified by propensity for treatment intensity demonstrated that those who received higher levels of antidepressant treatment were significantly more likely to recover from affective episodes. In contrast, those treated with lower levels were no more likely to recover than those who did not receive somatic treatment. CONCLUSIONS: Despite the indications of more severe depressive illness, those who received higher levels of somatic antidepressant treatment were more likely to recover from recurrent affective episodes. Results from this observational study extend the generalizability of reports from randomized clinical trials of antidepressants to a wider, more representative group of individuals who suffer from major depression.     

Desipramine-yohimbine combination treatment of refractory depression. Implications for the beta-adrenergic receptor hypothesis of antidepressant action

Preclinical investigations have shown that combined administration of the alpha 2-adrenergic receptor antagonist yohimbine hydrochloride and the tricyclic antidepressant desipramine hydrochloride produces a reduction in brain beta-adrenergic receptor function within four days. Since the ability of antidepressant treatments to reduce beta-adrenergic receptor function has been hypothesized to mediate antidepressant efficacy, it was predicted that combined desipramine-yohimbine treatment would be a more rapid-acting and potent antidepressant regimen than desipramine alone. In the present investigation, the effects of desipramine (N = 11) and desipramine-yohimbine (N = 10) treatment on depressive symptoms, norepinephrine turnover, and blood pressure were determined in patients with major depression who had a history of nonresponse to standard antidepressant treatments. Neither desipramine nor desipramine-yohimbine proved to be an effective treatment, although concomitant yohimbine administration did attenuate the ability of desipramine to decrease plasma free and 24-hour urinary 3-methoxy-4-hydroxyphenyl-ethyleneglycol levels and blood pressure. Fifteen of the 21 patients eventually had a good response to pharmacologic treatments, particularly a desipramine-lithium carbonate or lithium carbonate-tranylcypromine sulfate combination treatment (11 of 14 responded). This study provides evidence against the beta-adrenergic receptor hypothesis of antidepressant action.     

Lack of efficacy of estradiol for depression in postmenopausal women: a randomized, controlled trial.

BACKGROUND: Estrogen has been considered as a potential antidepressant in postmenopausal women. Our goal was to study whether estrogen therapy is effective in treating depressive disorders in older postmenopausal women and to determine whether progestins are associated with a deterioration of mood. METHODS: After 2 weeks of single-blind placebo treatment in 87 patients, 57 were randomly assigned to receive 8 weeks of treatment with estradiol (.1 mg/day; n = 31) or placebo (n = 26). All patients were then treated with medroxyprogesterone 10 mg/day for 2 weeks combined with the study patch. Depressive symptoms were rated with the 21-item Hamilton Depression and Center for Epidemiologic Studies Depression scales. RESULTS: A clinically significant antidepressant effect of estradiol was excluded after 8 weeks of estradiol treatment. The estradiol group and placebo group improved in depressive symptoms at a similar rate based on the Hamilton Depression Scale (40% decreases in depression for estradiol vs. 44% for placebo). No significant increase in depressive symptoms was demonstrated with the use of progestins; however, positive affect decreased slightly with the use of combined estradiol-medroxyprogesterone compared with medroxyprogesterone alone (5.8%, p =.027). CONCLUSIONS: Estradiol cannot be considered as an effective treatment in postmenopausal women with mild to moderate depression.     

Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment

Abnormal signal transduction pathways have been implicated in the pathogenesis of bipolar disorder and major depression. G-proteins are key elements of these pathways in the regulation of cellular responses by transmission of signals from receptors to effector proteins. In recent years several studies have reported altered levels and activities of G-protein alpha subunits in depressive patients. A recently identified polymorphism of a G-protein beta3 subunit (C825T) has been shown to be associated with increased signal transduction and ion transport activity. Therefore, we investigated whether this Gbeta3 polymorphism is associated with affective disorders or with the response to antidepressant treatment in 88 depressive patients (10 bipolar disorder, 78 major depression) compared with 68 schizophrenic patients and 111 healthy controls. We found a significantly higher frequency of the T allele in depressive patients than in healthy controls (genotype: chi2 = 9.571, df = 2, p = 0.008; alleles: p = 0.004, OR = 1.87, 95% CI 1.23-2.84; Fisher's exact test, two sided) and schizophrenic patients (genotype: chi2 = 8.037, df = 2, p = 0.018; alleles: p = 0.009, OR = 1.94, 95% CI 1.99-3.14; Fisher's exact test, two sided). We also found a statistical significant association between TT homozygosity and response to antidepressant treatment after four weeks (p = 0.01). The results of this study suggest that the investigated G-protein beta3 subunit seems to be a susceptibility factor for major depression and maybe even for bipolar disorder, but not for schizophrenia. Further, the presence of the T allele could be an indicator for treatment response.     

Double-blind treatment of major depression with dehydroepiandrosterone

OBJECTIVE: This study was designed to assess possible antidepressant effects of dehydroepiandrosterone (DHEA), an abundant adrenocortical hormone in humans. METHOD: Twenty-two patients with major depression, either medication-free or on stabilized antidepressant regimens, received either DHEA (maximum dose = 90 mg/day) or placebo for 6 weeks in a double-blind manner and were rated at baseline and at the end of the 6 weeks with the Hamilton Depression Rating Scale. Patients previously stabilized with antidepressants had the study medication added to that regimen; others received DHEA or placebo alone. RESULTS: DHEA was associated with a significantly greater decrease in Hamilton depression scale ratings than was placebo. Five of the 11 patients treated with DHEA, compared with none of the 11 given placebo, showed a 50% decrease or greater in depressive symptoms. CONCLUSIONS: These results suggest that DHEA treatment may have significant antidepressant effects in some patients with major depression. Further, larger-scale trials are warranted.     

A comparison of cognitive-behavioral therapy, sertraline, and their combination for adolescent depression

OBJECTIVE: To evaluate cognitive-behavioral therapy, antidepressant medication alone, and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents. METHOD: Seventy-three adolescents (ages 12-18 years) with a primary diagnosis of DSM-IV major depressive disorder, dysthymic disorder, or depressive disorder not otherwise specified were randomly allocated to one of three treatments. Treatment outcome measures were administered before and after acute treatment, and at a 6-month follow-up. Depression diagnosis was the primary outcome measure; secondary measures were self- and other report and clinician rating of global functioning. The trial was conducted at three community-based clinics between July 2000 and December 2002. Data analyses used an intent-to-treat strategy. RESULTS: Following acute treatment, all treatment groups demonstrated statistically significant improvement on outcome measures (depressive diagnosis, Reynolds Adolescent Depression Scale, Revised Children's Manifest Anxiety Scale, Suicidal Ideation Questionnaire), and improvement was maintained at follow-up. Combined cognitive-behavioral therapy and antidepressant medication was not found to be superior to either treatment alone. Compared with antidepressant medication alone, participants receiving cognitive-behavioral therapy alone demonstrated a superior acute treatment response (odds ratio = 6.86; 95% confidence interval 1.12-41.82). Although cognitive-behavioral therapy was found to be superior to antidepressant medication alone for the acute treatment of mild to moderate depression among youth, this may have stemmed from the relatively low dose of sertraline used. CONCLUSIONS: All treatments led to a reduction in depression, but the advantages of a combined approach were not evident.     

Antidepressant effect of femoxetine and desipramine and relationship to the concentration of amine metabolites in cerebrospinal fluid

The antidepressant and biochemical effects of femoxetine, a selective serotonin uptake inhibitor, and desipramine, a selective nor-adrenaline uptake inhibitor, have been compared in a double–blind study in 42 outpatients with depressive illness. The patients were allocated at random to treatment with either 600 mg femoxetine or 150 mg desipramine daily for 6 weeks. The total depression score showed a significant decrease in both groups, indicating an overall improvement in depressive symptoms. The patients treated with femoxetine reported significantly less severe anticholinergic effects during the whole treatment period than the desipramine patients. Both drugs decreased the level of 5-HIAA in CSF, whereas no consistent changes were found in the HMPG and HVA levels. The pretreatment level of the metabolites had no predictive value for the outcome of the treatment with either drug. No significant correlation was found between therapeutic effect and the plasma concentration of the active compounds.     

The impact of antidepressant discontinuation versus antidepressant continuation on 1-year risk for relapse of bipolar depression: a retrospective chart review

BACKGROUND: Current treatment guidelines recommend discontinuation of an antidepressant within 3 to 6 months after remission of depression in patients with bipolar illness. Yet few studies directly compare the impact of antidepressant discontinuation versus antidepressant continuation on the risk for depressive relapse in patients with bipolar disorder who have been successfully treated for a depressive episode. METHOD: In a retrospective chart review, patients with DSM-IV bipolar disorder who were treated for an index episode of depression by adding antidepressant medication to ongoing mood stabilizer medications were identified. The risk of depressive relapse in 25 subjects who stopped antidepressant medications after improvement was compared with the risk of depressive relapse in 19 subjects who continued antidepressants after improvement. RESULTS: Termination of antidepressant medication significantly increased the risk of a depressive relapse. Antidepressant continuation was not significantly associated with an increased risk of mania. CONCLUSION: While this study may have been limited by the retrospective nature of the chart review, nonrandomized assignment of treatment, and reliance on unstructured progress notes, it suggests that antidepressant discontinuation may increase the risk of depressive relapse in some patients with bipolar disorder. Further research is needed to clarify whether maintenance antidepressant treatment may be warranted in some patients with bipolar disorder, especially in those with frequent recurrent depressive episodes.     

Anger attacks in major depressive disorder and serum levels of homocysteine.

BACKGROUND: Increased levels of homocysteine have been associated with anger and depression separately. We investigated the association of anger attacks in major depressive disorder (MDD) with serum levels of homocysteine. METHODS: Homocysteine serum levels were measured in 192 outpatients with nonpsychotic MDD, mean age 39.9 +/- 10.7 (range 19-65), 53% women, at baseline of an open-trial antidepressant treatment. We used the Massachusetts General Hospital Anger Attacks Questionnaire to evaluate anger attacks, the Structured Clinical Interview for DSM-III-R Axis I Disorders-Patient Edition (SCID-I/P) to diagnose MDD and the 17-item Hamilton Rating Scale for Depression to measure depression severity. RESULTS: In the multiple regression analysis split by anger attacks adjusted for parameters of depression, creatinine, vitamin B(12), folate, age, smoking, and alcohol consumption, serum levels of homocysteine were positively correlated with length of current major depressive episode (t value, 3.01; 95% confidence interval [CI], .09 to .43; p = .004) and HAM-D-17 scores (t value, 2.48; 95% CI, .07 to 0.64; p = .016) in patients with anger attacks but not in those without anger attacks. CONCLUSIONS: Anger attacks in MDD may moderate the relationship of homocysteine serum levels with the severity and length of the depressive episode. Future studies are warranted to confirm and clarify the nature of this moderating effect.     

Late-life depression and mortality: influence of gender and antidepressant use

BACKGROUND: Depression may increase the risk of mortality among certain subgroups of older people, but the part played by antidepressants in this association has not been thoroughly explored. AIMS: To identify the characteristics of older populations who are most at risk of dying, as a function of depressive symptoms, gender and antidepressant use. METHOD: Adjusted Cox proportional hazards models were used to determine the association between depression and/or antidepressant use and 4-year survival of 7,363 community-dwelling elderly people. Major depressive disorder was evaluated using a standardised psychiatric examination based on DSM-IV criteria and depressive symptoms were assessed using the Center for Epidemiological Studies-Depression scale. RESULTS: Depressed men using antidepressants had the greatest risk of dying, with increasing depression severity corresponding to a higher hazard risk. Among women, only severe depression in the absence of treatment was significantly associated with mortality. CONCLUSIONS: The association between depression and mortality is gender-dependent and varies according to symptom load and antidepressant use.     

Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects

OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings.     

Anxiety and depression in young physicians: Prevalence and associated factors. The MESSIAEN national study

BackgroundPhysicians are at risk of anxiety and depression.ObjectivesTo determine the prevalence of anxiety and depression in a national sample of young physicians and their associated factors.MethodsThe study is a cross-sectional observational epidemiological national study. An online anonymous questionnaire was administered to the young physicians of all French medical faculties. Anxiety and depression were assessed with the Hamilton Anxiety & Depression scale subscores for anxiety and depression. Psychotropic drug consumption, psychotherapy follow-up and other variables were self-declared.ResultsOf the 2003 study participants, 32.3% reported a current anxiety disorder and 8.7% a current major depressive disorder according to their HAD scores and less than one on five of them was followed-up in psychotherapy or treated by antidepressant. Moral harassment, a bad quality of initial formation regarding dealing with disease and alcohol consumption were all associated with respectively anxiety disorder and major depression in multivariate analyses. Medical vocation was specifically associated with decreased major depression while being woman and increased coffee consumption were specifically associated with increased anxiety disorders.ConclusionAlmost one third of medical students reported anxiety disorder or major depression and less than one on five received the recommended treatment (psychotherapy or antidepressant). The prevention and treatment of psychiatric disorders should be improved in this population. Moral harassment exposure, alcohol and coffee consumptions, bad quality of initial formation regarding dealing with disease have been identified as modifiable factors associated with poor mental health. Despite the absence of causal associations, these results yield some clues to guide future mental health prevention strategies in this population.