Relationship of suicide rates with climate and economic variables in Europe during 2000-2012.

BACKGROUND: It is well known that suicidal rates vary considerably among European countries and the reasons for this are unknown, although several theories have been proposed. The effect of economic variables has been extensively studied but not that of climate. METHODS: Data from 29 European countries covering the years 2000-2012 and concerning male and female standardized suicidal rates (according to WHO), economic variables (according World Bank) and climate variables were gathered. The statistical analysis included cluster and principal component analysis and categorical regression. RESULTS: The derived models explained 62.4 % of the variability of male suicidal rates. Economic variables alone explained 26.9 % and climate variables 37.6 %. For females, the respective figures were 41.7, 11.5 and 28.1 %. Male suicides correlated with high unemployment rate in the frame of high growth rate and high inflation and low GDP per capita, while female suicides correlated negatively with inflation. Both male and female suicides correlated with low temperature. DISCUSSION: The current study reports that the climatic effect (cold climate) is stronger than the economic one, but both are present. It seems that in Europe suicidality follows the climate/temperature cline which interestingly is not from south to north but from south to north-east. This raises concerns that climate change could lead to an increase in suicide rates. The current study is essentially the first successful attempt to explain the differences across countries in Europe; however, it is an observational analysis based on aggregate data and thus there is a lack of control for confounders.

Relationship of suicide rates to economic variables in Europe: 2000-2011.

BACKGROUND: It is unclear whether there is a direct link between economic crises and changes in suicide rates. AIMS: The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates. METHOD: Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation. RESULTS: There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged. CONCLUSIONS: Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.

Lithium toxicity profile: a systematic review and meta-analysis.

BACKGROUND: Lithium is a widely used and effective treatment for mood disorders. There has been concern about its safety but no adequate synthesis of the evidence for adverse effects. We aimed to undertake a clinically informative, systematic toxicity profile of lithium. METHODS: We undertook a systematic review and meta-analysis of randomised controlled trials and observational studies. We searched electronic databases, specialist journals, reference lists, textbooks, and conference abstracts. We used a hierarchy of evidence which considered randomised controlled trials, cohort studies, case-control studies, and case reports that included patients with mood disorders given lithium. Outcome measures were renal, thyroid, and parathyroid function; weight change; skin disorders; hair disorders; and teratogenicity. FINDINGS: We screened 5988 abstracts for eligibility and included 385 studies in the analysis. On average, glomerular filtration rate was reduced by -6·22 mL/min (95% CI -14·65 to 2·20, p=0·148) and urinary concentrating ability by 15% of normal maximum (weighted mean difference -158·43 mOsm/kg, 95% CI -229·78 to -87·07, p<0·0001). Lithium might increase risk of renal failure, but the absolute risk was small (18 of 3369 [0·5%] patients received renal replacement therapy). The prevalence of clinical hypothyroidism was increased in patients taking lithium compared with those given placebo (odds ratio [OR] 5·78, 95% CI 2·00-16·67; p=0·001), and thyroid stimulating hormone was increased on average by 4·00 iU/mL (95% CI 3·90-4·10, p<0·0001). Lithium treatment was associated with increased blood calcium (+0·09 mmol/L, 95% CI 0·02-0·17, p=0·009), and parathyroid hormone (+7·32 pg/mL, 3·42-11·23, p<0·0001). Patients receiving lithium gained more weight than did those receiving placebo (OR 1·89, 1·27-2·82, p=0·002), but not those receiving olanzapine (0·32, 0·21-0·49, p<0·0001). We recorded no significant increased risk of congenital malformations, alopecia, or skin disorders. INTERPRETATION: Lithium is associated with increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain. There is little evidence for a clinically significant reduction in renal function in most patients, and the risk of end-stage renal failure is low. The risk of congenital malformations is uncertain; the balance of risks should be considered before lithium is withdrawn during pregnancy. Because of the consistent finding of a high prevalence of hyperparathyroidism, calcium concentrations should be checked before and during treatment. FUNDING: National Institute for Health Research Programme Grant for Applied Research.

Insight in schizophrenia: from conceptualization to neuroscience.

Lack of insight into illness is a prevalent and distinguishing feature of schizophrenia, which has a complex history and has been given a variety of definitions. Currently, insight is measured and treated as a multidimensional phenomenon, because it is believed to result from psychological, neuropsychological and organic factors. Thus, schizophrenia patients may display dramatic disorders including demoralization, depression and a higher risk of suicide, all of which are directly or indirectly related to a lack of insight into their illness, and make the treatment difficult. To improve the treatment of people with schizophrenia, it is thus crucial to advance research on insight into their illness. Insight is studied in a variety of ways. Studies may focus on the relationship between insight and psychopathology, may view behavioral outcomes or look discretely at the cognitive dysfunction versus anatomy level of insight. All have merit but they are dispersed across a wide body of literature and rarely are the findings integrated and synthesized in a meaningful way. The aim of this study was to synthesize findings across the large body of literature dealing with insight, to highlight its multidimensional nature, measurement, neuropsychology and social impact in schizophrenia. The extensive literature on the cognitive consequences of lack of insight and the contribution of neuroimaging techniques to elucidating neurological etiology of insight deficits, is also reviewed.

Differential responses to emotional interference in paranoid schizophrenia and bipolar mania.

BACKGROUND: Studies on emotional biases towards threat-related stimuli in schizophrenia and bipolar disorder have provided, so far, inconsistent results. The aim of the present study was to investigate emotional interference in acute schizophrenic and manic patients and its clinical correlates by using a card version of the Emotional Stroop Task designed with neutral, paranoid, depressive and manic words. METHODS: Thirty paranoid schizophrenia patients, 30 manic patients and 60 healthy controls were compared on the Emotional Stroop Test. Response times (RT) were collected for each card. Interference indices were calculated by subtracting the RT for the neutral card from the RT for the depressive, paranoid and manic cards. RESULTS: The schizophrenic and manic patient groups showed an increased interference effect when the emotional valence was relating to the disorder-specific psychopathology. In addition, the paranoid interference index correlated with positive symptoms in schizophrenic patients. By contrast, no correlation was evidenced between interference indices and mood symptoms in the manic group. CONCLUSIONS: Among schizophrenic patients, paranoid interference might be a state-related emotional abnormality associated with persecutory delusions. In mania, we suggest that emotional biases towards depressive as well as manic information might be trait features of the emotional hyperreactivity involved in the vulnerability to bipolar disorder.

Risk factors associated with lifetime suicide attempts in bipolar I patients: findings from a French National Cohort.

Risk factors that may be associated with suicide attempts in bipolar disorder are still a matter of debate. We compared demographic, illness course, clinical, and temperamental features of suicide attempters vs those of nonattempters in a large sample of bipolar I patients admitted for an index manic episode. One thousand ninety patients (attempters = 382, nonattempters = 708) were included in the study. Multivariate analysis evidenced 8 risk factors associated with lifetime suicide attempts as follows: multiple hospitalizations, depressive or mixed polarity of first episode, presence of stressful life events before illness onset, younger age at onset, no free intervals between episodes, female sex, higher number of previous episodes, and cyclothymic temperament. These characteristics may help identify subjects at risk for suicide attempt throughout the course of bipolar disorder. We finally propose to integrate such characteristics into a stress-diathesis model of suicidal behavior, adapted to bipolar patients.

Psychopathological correlates of lifetime anxiety comorbidity in bipolar I patients: findings from a French national cohort.

BACKGROUND: Despite numerous studies on the comorbidity of bipolar and anxiety disorders, there is no satisfactory psychopathological model for their overlap. METHOD: 1,090 hospitalized patients meeting DSM-IV criteria for a manic episode of bipolar I disorder were subtyped according to the presence or not of lifetime anxiety comorbidity and assessed for demographic, illness course, clinical, associated condition, temperament, and treatment characteristics. RESULTS: Lifetime anxiety comorbidity, defined as presence of at least one anxiety disorder in lifetime, was found in 27.2% (n = 297) of the sample. Compared to patients without such a comorbidity (n = 793), those who had it experienced a higher number of mood episodes and suicide attempts in the previous year, more stressors, organic disorders and less free intervals; furthermore, they showed more temperaments with depressive features and complex treatment. At study entry, they also experienced manic episodes with higher levels of depression, psychosis and hostility. The following independent variables were associated with lifetime anxiety comorbidity: higher scores on the Montgomery-Asberg Depression Rating Scale, depressive temperament, irritable temperament, higher scores on the Scale for the Assessment of Positive Symptoms, episodes without free intervals and at least one stressor before the index episode. CONCLUSIONS: Factors associated with lifetime anxiety comorbidity in bipolar I patients may be integrated into a comprehensive diathesis-stress model emphasizing the role of irritable temperament as a source of mood instability and stress, and interacting with other temperamental characteristics to trigger the outbreak of both anxiety and bipolar symptoms.

Lack of insight may predict impaired decision making in manic patients.

OBJECTIVES: The tendency to engage in risky behaviours is a core feature of the manic episodes of bipolar disorder. The aim of this study was to establish whether this characteristic can be quantified with a laboratory measure of decision making [the Iowa Gambling Task (IGT)] and to determine clinical correlates of the IGT performance in mania. METHODS: Inpatients with acute mania (n = 45) and healthy volunteers (n = 45) were assessed on the IGT. Affective symptomatology was assessed with the Young Mania Rating Scale and Hamilton Depression Rating Scale, and item scores were subjected to factor analysis. Multivariate regression was used to assess clinical predictors of impaired decision making in the manic patients. RESULTS: On the IGT, manic patients selected more cards from the risky decks than healthy controls, and showed little capacity to learn from incurred losses. In a multivariate analysis, impaired decision making ability in the manic patients was significantly predicted by a symptom factor associated with lack of insight. CONCLUSIONS: Manic patients clearly show defects in decision making, which are strongly related to their lack of insight. Neural circuitry supporting effective decision making, including the ventromedial prefrontal cortex and somatosensory cortex, may be implicated in the pathophysiology of acute mania.

Factors associated with rapid cycling in bipolar I manic patients: findings from a French national study.

INTRODUCTION: Despite numerous explanatory hypotheses, few studies have involved a large national clinical sample examining risk factors in the occurrence of rapid cycling during the course of bipolar illness. METHODS: From 1,090 manic bipolar I disorder inpatients included in a multicenter national study in France, 958 could be classified as rapid or nonrapid cyclers and assessed for demographic, illness course, clinical, psychometric, temperament, comorbidity, and treatment characteristics. RESULTS: Rapid cycling bipolar disorder occurred in 9% (n=86) of the study group. Compared to nonrapid cyclers (n=872), patients with rapid cycling experienced the onset of their illness at a younger age, a higher number of prior episodes, more depression during the first episode, and more suicide attempts. At study entry, they also experienced manic episodes with more depressive and anxious symptoms, but less psychotic features. The following independent variables were associated with rapid cycling: longer duration of illness, antidepressant treatment, episodes with no free intervals, cyclothymic temperament, lower scores on the Scale for Assessment of Positive Symptoms and presence of thyroid disorder. Retrospective study limited to bipolar I disorder inpatients; several factors previously associated with rapid cycling were not assessed. CONCLUSION: Our findings may confirm previous descriptions, according to which rapid cycling develops later in the course of illness following a sensitization process triggered by antidepressant use or thyroid dysfunction, in patients with a depression-mania-free interval course, and cyclothymic temperament.

Toward the delineation of mania subtypes in the French National EPIMAN-II Mille Cohort. Comparisons with prior cluster analytic investigations.

BACKGROUND: Knowledge about psychopathologic presentations of mania in current clinical practice has to be refined in order to improve diagnosis and treatment. METHODS: One thousand ninety manic patients included in the French National Study EPIMAN-II Mille were submitted to a cluster analysis on the basis of multiple variables related to the history of bipolar illness and symptoms of the current episode. RESULTS: Four clusters were identified: "classic mania" (29.3% of patients) with less severe mania; "psychotic mania" (22.7%) with psychotic symptoms, more severe mania, younger age and social impairment; "depressive mania" (30.4%) characterized by female gender, suicide attempts, high number of previous episodes and residual symptoms; and "dual mania" (17.6%) characterized by male gender, substance use, earlier onset and poor compliance. Patients groups also differed in manic symptoms, marital status, stressors preceding illness onset, prior diagnoses, first episode polarity and temperamental characteristics. LIMITATIONS: Cross-sectional assessment of patients. CONCLUSIONS: In comparing our findings with those of four prior cluster analytic studies, we integrate clinical characteristics of mania subtypes found in this very large representative French sample in contemporary practice, we suggest how such convergence of data may help improve earlier recognition, differential response to different treatments, and prevention of these subtypes. We finally suggest that such subtyping might provide clues to phenotype delineation suitable for pharmacogenetic investigations.

Alcohol use and bipolar disorders: Risk factors associated with their co-occurrence and sequence of onsets.

BACKGROUND: Little is known about the sequence of onsets in patients affected by comorbid alcohol use and bipolar disorder. This study examines the risk factors associated with their co-occurrence and order of onset. METHOD: The demographic, clinical, and temperament characteristics as well as the course of illness were analyzed within our sample of 1090 DSM-IV bipolar I manic patients. Our sample was categorized according to the presence of comorbid alcohol use disorder and the sequence of onsets of bipolar and alcohol use disorders i.e., alcohol first (AUD-BD) and bipolar first (BD-AUD). RESULTS: Regression analyses revealed that alcohol use disorder (52.5%) was associated with the male gender, additional substance use disorders, as well as an irritable and a hyperthymic temperament. The AUD-BD group (6.6%) was older than the BD-AUD group (45.8%) and showed higher rates of comorbid sedative use, organic, and anxiety disorders with higher levels of irritable temperament, and a bipolar subtype characterized by depressive polarity at onset. The BD-AUD group had high levels of hyperthymic temperament with higher rates of comorbid stimulant use disorder and a manic polarity at onset. CONCLUSIONS: In the AUD-BD group, alcohol might have been used to reduce stress and tension caused by the presence of an irritable temperament as well as anxious and organic disorders, leading to first depressive episode. In the BD-AUD group, stimulant use might have triggered the first manic episode, and alcohol abuse result from mania severity.

Pharmacological treatment of schizophrenia with comorbid substance use disorder.

INTRODUCTION: While antipsychotics remain the cornerstone of treatment for schizophrenic patients with comorbid substance use disorder (SUD), such treatment is nonetheless complicated by frequent medical comorbidity and poor adherence to medication. AREAS COVERED: Randomised controlled trials (RCTs) on the efficacy of antipsychotics for the treatment of schizophrenic patients with comorbid SUD are reviewed and analysed on the basis of a systematic literature search (PubMed) ranging from 1985 to 2015. On the same basis, findings from RCTs on the efficacy of psychotropic and other medications used for primary SUD are summarised, and the main issues liable to influence treatment choice are discussed, including pharmacodynamic as well as pharmacokinetic interactions, adherence, medical comorbidity and the impact on brain structure. EXPERT OPINION: As far as the treatment of schizophrenic patients with SUD is concerned, direct and indirect evidence tends to stand in favour of the use of second-generation antipsychotics (SGAs), and particularly those with lower metabolic, cardiovascular and extrapyramidal side effects, as well as those with a depot formulation. A few of the usual medications for the treatment of primary SUD, such as naltrexone and disulfiram for alcohol use and bupropion for tobacco cessation, can also be safely and efficiently administered to schizophrenic patients with SUD.

Frequency and characteristics of individuals with seasonal pattern among depressive patients attending primary care in France.

OBJECTIVE: High rates of bipolar disorder (BD) have been found among major depressives with seasonal pattern (SP) consulting in psychiatric departments, as well as among patients seeking primary care. As SP was reported to be common in the latter, the current study was designed to assess (a) the frequency and characteristics of SP among major depressives attending primary care and (b) the prevalence and aspects of BD in this population. METHODS: Among 400 patients who consulted French general practitioners (GPs) for major depression between February and December 2010, 390 could be included in the study: 167 (42.8%) met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for seasonal pattern [SP(+)], whereas 223 (57.2%) did not meet these criteria [SP(-)]. The two groups were compared on demographic, clinical, family history and temperamental characteristics. RESULTS: Compared to SP(-), SP(+) patients were more frequently female, married and with a later age at first depressive episode, and showed more atypical vegetative symptoms, comorbid bulimia and stimulant abuse. They also exhibited more lifetime depressive episodes, were more often diagnosed as having BD II and met more often bipolarity specifier criteria, with higher rates of bipolar temperaments and a higher BD family loading. Among SP(+) patients, 68.9% met the bipolarity specifier criteria, whereas 31.1% did not. Seasonality was not influenced by climatic conditions. The following independent variables were associated with SP: BD according to bipolarity specifier, female gender, comorbid bulimia nervosa, hypersomnia, number of depressive episodes and family history of substance abuse. CONCLUSIONS: Seasonal pattern is frequent among depressive patients attending primary care in France and may be indicative of hidden bipolarity. Given the risks associated with both SP and bipolarity, GPs are likely to have a major role in regard to prevention.

Age-at-onset and comorbidity may separate depressive disorder subtypes along a descending gradient of bipolar propensity.

Depressive illnesses with subthreshold bipolar features are still misdiagnosed as unipolar. The goal of this study was to identify depressive disorder subtypes at risk for bipolarity. Four hundred ninety three major depressive patients were submitted to a cluster analysis on the basis of affective illness history and symptoms of the current episode. Seven clusters were identified which were regrouped into three age-at-onset subgroups; subgroups were further differentiated into subtypes according to predominant comorbidities. The latter were found to precede the occurrence of the related depressive disorder subtypes, decrease their age-at-onset, and increase their risk of belonging to the bipolar spectrum: the earlier the comorbidity, the higher the bipolar propensity was. This is likely to have implications for the diagnosis, natural history, as well as prophylaxis of bipolar disorders.

Lithium might be associated with better decision-making performance in euthymic bipolar patients.

Bipolar disorder is associated with impaired decision-making. Little is known about how treatment, especially lithium, influences decision-making abilities in bipolar patients when euthymic. We aimed at testing for an association between lithium medication and decision-making performance in remitted bipolar patients. Decision-making was measured using the Iowa Gambling Task in 3 groups of subjects: 34 and 56 euthymic outpatients with bipolar disorder, treated with lithium (monotherapy and lithium combined with anticonvulsant or antipsychotic) and without lithium (anticonvulsant, antipsychotic and combination treatment), respectively, and 152 matched healthy controls. Performance was compared between the 3 groups. In the 90 euthymic patients, the relationship between different sociodemographic and clinical variables and decision-making was assessed by stepwise multivariate regression analysis. Euthymic patients with lithium (p=0.007) and healthy controls (p=0.001) selected significantly more cards from the safe decks than euthymic patients without lithium, with no significant difference between euthymic patients with lithium and healthy controls (p=0.9). In the 90 euthymic patients, the stepwise linear multivariate regression revealed that decision-making was significantly predicted (p<0.001) by lithium dose, level of education and no family history of bipolar disorder (all p≤0.01). Because medication was not randomized, it was not possible to discriminate the effect of different medications. Lithium medication might be associated with better decision-making in remitted bipolar patients. A randomized trial is required to test for the hypothesis that lithium, but not other mood stabilizers, may specifically improve decision-making abilities in bipolar disorder.

Effectiveness of methylphenidate as augmentation therapy after failure of adjunctive neuromodulation for patients with treatment-refractory bipolar depression: a case report.

Adjunctive use of methylphenidate, a central stimulant, has been considered as a potential therapeutic choice for patients with refractory unipolar, geriatric, or bipolar depression, and depression secondary to medical illness. We present a case of bipolar depression in which the patient responded significantly to augmentation with methylphenidate, without any side effects, after failure of adjunctive repetitive transcranial magnetic stimulation and electroconvulsive therapy. Mr U, a 56-year-old man with bipolar I disorder, had melancholic symptoms during his sixth episode of bipolar depression. After failure of repetitive transcranial magnetic stimulation and electroconvulsive therapy, he was treated with fluoxetine 80 mg/day, duloxetine 360 mg/day, mirtazapine 60 mg/day, and sodium valproate 1,000 mg/day, with no improvement. We added methylphenidate at a dose of 10 mg/day for one week, which resulted in mild clinical improvement, and then methylphenidate extended-release 20 mg/day for one week, with significant clinical improvement. He tolerated his medications well. His clinical recovery was stable over one year. The patient's antidepressants and methylphenidate were gradually tapered and finally discontinued after one year with no withdrawal syndrome. To date, he remains well on sodium valproate as monotherapy and is being followed up at our bipolar department. This case suggests that methylphenidate augmentation might be a therapeutic option when treating highly treatment-resistant patients with bipolar depression, even if they had not responded to adjunctive neuromodulation. In these clinical situations, physicians might be interested in prescribing methylphenidate because of its efficacy and safety.

Negative Symptoms in Schizophrenia: Where We have been and Where We are Heading.

This review traces the history of negative symptom profiles in neuropsychiatry from their earliest emergence in the 19th century to the current psychiatric concepts and therapeutic approaches. Recent investigations performing exploratory and confirmatory factor analysis have suggested that negative symptoms are multidimensional, including evidence for at least two distinct negative symptom subdomains: diminished expression and amotivation. Preliminary studies have demonstrated the clinical validity of this distinction. Several potential pathophysiological validating factors based on brain imaging analysis of emotional experiences and expressions in individuals with schizophrenia are examined. Finally, the potential of different treatment strategies, including medications and various psychotherapeutic techniques, to most favorably treat each of these subdomains is discussed.

[Ketamine in acute and severe major depressive disorder]. / La kétamine dans le traitement du trouble dépressif aigu sévère.

CONTEXT: Depression is a frequent, severe and expensive illness. Approximately 20% of depressive episodes are resistant to classic antidepressants. Glutamatergic antagonists, in particular ketamine, established a new, rapid and robust therapeutic approach in resistant depression. RESULTS: The main results in the literature show a rapid and robust antidepressant effect of ketamine, with infra-anesthesic posology (0.5mg/kg) administered in intravenous way. Positive effects are observed on depressive symptoms, suicidal thoughts, and there is a potential synergic action when used in the induction of anesthesia for electroconvulsive therapy. However, effects only last shortly. Side effects are mostly reversible and of mild intensity, no severe consequences were reported. LIMITS: Limits are the lack of power of the included studies, due to small sample sizes, and the scarcity of studies. Misuse of ketamine is an important issue to be taken into account, and few data about ketamine addiction potential and its long-term effects are published at the moment.

Gender differences in a cohort of major depressive patients: further evidence for the male depression syndrome hypothesis.

BACKGROUND: Previous studies have shown that major depressive patients may differ in several features according to gender, but the existence of a specific male depressive syndrome remains controversial. METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 125 (27.7%) were of male gender, whereas 317 (72.3%) were female, after exclusion of bipolar I patients. RESULTS: Compared to women, men were more often married, had more associated mixed features, with more bipolar disorder NOS, more hyperthymic temperaments, and less depressive temperaments. Women had an earlier age at onset of depression, more depressive episodes and suicide attempts. A higher family loading was shown in men for bipolar disorder, alcohol use disorder, impulse control disorders and suicide, whereas their family loading for major depressive disorder was lower. Men displayed more comorbidities with alcohol use, impulse control, and cardiovascular disorders, with lower comorbidities with eating, anxiety and endocrine/metabolic disorders. The following independent variables were associated with male gender: hyperthymic temperament (+), alcohol use disorder (+), impulse control disorders (+), and depressive temperament (-). LIMITATIONS: The retrospective design and the lack of specific tools to assess the male depressive syndrome. CONCLUSION: Study findings may lend support to the male depression syndrome concept and draw attention to the role of hyperthymic temperament, soft bipolarity as well as comorbidities as determinants of this syndrome. The latter could help recognize an entity which is probably underdiagnosed, but conveys a high risk of suicide and cardiovascular morbidity.

[Psychostimulants in the treatment of depression]. / Psychostimulants dans le traitement de la dépression.

Psychostimulants promote alertness and reduce fatigues that have suggested their use in the treatment of depressive disorders in the early part of the 20th century. Overall, data support the use of psychostimulants in depression particularly in cases of drug resistance, when there is a severe physical illness or when short-term efficiency is needed, especially in the elderly. Psychostimulants are relatively better tolerated than conventional antidepressants, side effects concern less than 20% of patients. Nevertheless, they have to be prescribed carefully in front of the increased cases of misuse described by the literature and the French national committee of narcotics and psychotropics. Larger randomized, controlled trials with longer follow-up periods are needed to clarify a profile of response to psychostimulants, and assess the risk of developing tolerance or dependence on these substances.