Low blood pressure and risk of depression in the elderly. A prospective community-based study.

BACKGROUND: The relationship between depression and low blood pressure in unclear. AIMS: To examine the temporal relation between low blood pressure and depression in a two-year follow-up. METHOD: The study group consisted of 1389 subjects aged 59-71 years; 1272 (92%) were examined after two years. Subjects completed the Center for Epidemiological Studies-Depression (CES-D) and the Spielberger inventory scales to assess depressive and anxiety symptoms respectively. Data were collected on socio-demographic characteristics, smoking and drinking habits, medical history, drug use and blood pressure measures. RESULTS: Among 1112 subjects who were considered as non-depressed at baseline, logistic regression models showed that low diastolic blood pressure (DBP) and decrease of blood pressure were predictors of high depressive symptomatology at follow-up. Baseline high CES-D scores did not predict low blood pressure two years after. CONCLUSIONS: In our study, low blood pressure was a risk factor for, but not a consequence of, high depressive symptomatology.

Milnacipran efficacy in the prevention of recurrent depression: a 12-month placebo-controlled study. Milnacipran recurrence prevention study group.

To compare the efficacy and assess the tolerability of milnacipran 50mg p.o. b.i.d. to placebo in the prevention of recurrence in depressed patients who had responded an acute treatment and had remained in remission during a 4-month continuation phase. Remission criteria were: a Hamilton Depression Rating Scale (HDRS) (21-item) < or = 8, improvement or disappearance of the initial symptoms, and an assessment of 'very much improved' or 'much improved' on the Clinical Global Impression (CGI) Subscale: Global Improvement. Recurrence was defined by a major depressive episode according to DSM-III-R criteria and a minimum score of 18 on the HDRS, with the need to treat the recurrence. The primary analysis was the rate of recurrence as a function of time in the intent-to-treat population. Groups were compared using the Cox model. Absolute recurrence rates were 16.3% (17/104) in milnacipran-treated patients and 23.6% (26/110) in placebo-treated patients, with a significant difference in the reduction of recurrence as a function of time (Kaplan Meier Survival Analysis analysis, P < 0.05). There was no difference in tolerability between groups. This study demonstrates that milnacipran is effective with good tolerability in preventing recurrence in major depressive disorder over 1 year in patients with recurrent depression who responded to acute treatment with milnacipran and continued their response for 18 weeks.

Prevention of recurrent depressive episodes with milnacipran: consequences on quality of life.

BACKGROUND: Depression is now seen as a chronic disabling condition that spans the patient's lifetime and creates significant medical, economic and quality of life consequences. METHODS: 500 depressed patients were treated with milnacipran for 6 months. A total of 214 recovered patients were randomised to receive either milnacipran (50 mg bid) or a matching placebo for a 1-year recurrence prevention phase. Recurrence rate was the primary criteria; quality of life (QoL) consequences were evaluated through a shortened version of the French Sickness Impact Profile (SIP), the Depression Impact Profile (DIP). RESULTS: Milnacipran demonstrated its ability to reduce recurrences (Odds-Ratio=1.5; P<0.05), with a more marked effect in recovered patients with few residual symptoms (Odds-Ratio=3.0). Responders who continued treatment with milnacipran had a dramatic improvement in their quality of life, although patients with residual symptoms still experienced some deterioration in their QoL (recreation, emotional, social, alertness and home assistance scores). Even recovered patients having zero scores on the Hamilton Depression Rating Scale-21 items (HDRS) had some QoL deterioration. The DIP emotional score was found to be more predictive of recurrence than the HDRS. Overall, the QoL was improved for those in the milnacipran group in comparison to placebo on the mobility, communication, psycho-social and total scores. LIMITATIONS: The QoL evaluation was a secondary criteria; no a priori sample size estimate was performed. The choice of a generic QoL instrument might have reduced the sensitivity to clinical changes in depression. CONCLUSIONS: Prevention of recurrence in MDD with milnacipran contributes to an improvement in the QoL.

Economic assessment of a maintenance treatment strategy in prevention of recurrent depressive disorder.

OBJECTIVE: To compare the 12-month cost-effectiveness of milnacipran in maintenance treatment of depression to that of medical follow-up without antidepressant. METHOD: A Markov model with transition probabilities from a double blind clinical trial demonstrating the prophylactic efficacy of milnacipran was used. Other parameters were obtained from published sources. RESULTS: Base-case incremental cost for preventive treatment was 1,191 FF. It was reduced to 685 FF when using a 25% hospitalization rate in case of recurrence. Patients with a high initial response had extra cost of 191 FF and cost-utility was estimated to be 23,875 FF per QALY gained. For those patients, using a 25% hospitalization rate in case of recurrence, costs were lower at 1,174 FF and preventive strategy was dominating. CONCLUSION: Cost of maintenance therapy is partially balanced by the gain from recurrence prevention. It should be focused on patients with few residual symptoms or a high probability of hospitalization in case of recurrence.

[Clinico-economic assessment of milnacipran in the prevention of depressive episodes]. / Evaluation médico-économique de milnacipran dans la prévention des épisodes dépressifs.

The objective of this study was to evaluate, for patients at risk of a new depressive episode, the net cost of maintenance therapy with milnacipran compared with a symptomatic treatment of further episodes. Using clinical decision analysis techniques, a Markov-state transition was constructed to estimate the 12 months direct costs of the two therapeutic strategies. Model construction and probabilities for performing the analysis were primarily based on a controlled phase III clinical trial demonstrating the prophylactic efficacy of milnacipran compared to placebo. Others parameters and unit costs were obtained from published sources. For each group (maintenance and episodic treatment groups), the model simulated the clinical evolution of patients on 6 successive 2-months cycles. Costs were affected for each health state period (remission, depression, abandonment of health care, suicide). The baseline analysis showed the mean costs per patient and year were 627 FF (105 US$) higher for maintenance treatment. Sensitivity analysis suggested that costs were equal under a 25% rate of hospitalization hypothesis for a depressive episode. Maintenance costs were 1,587 FF (265 US$) lower than episodic treatment costs for depressed subjects with a good initial response to milnacipran (HDRS-21 score at remission < 5); this economic benefit remained under a lower rate of hospitalization hypothesis (12%). Based on the study assumptions, maintenance treatment with milnacipran appears to be clinically and economically justified for patients at high risk of hospitalization when having a recurrence, and even more for patients with an excellent initial acute response.

Anxiolytic and hypnotic use in 376 psychiatric inpatients. GERMED Neuropsychotropics Group.

This objectives of this study were three-fold: retrospectively evaluate anxiolytic/hypnotic consumption by psychiatric inpatients, identify the risk factors of prolonged intakes, and prospectively measure the impact of hospitalisation on the use of those drugs. Three hundred and seventy-six patients hospitalised in 11 psychiatric departments in the Paris region were studied using a structured interview for the anxiolytic/hypnotic treatments, DSM-III-R criteria, GHQ-12, HAD, Spiegel's questionnaire, COVI's anxiety scale and the CGI. Eighty-five per cent of the patients had taken one anxiolytic/hypnotic or more in the 3 months preceding hospitalisation. Hospitalisation induced little change in anxiolytic/hypnotic use: dosage frequency increased from 77% to 84% between the week preceding hospitalisation and that preceding discharge; 26% of consumers were taking at least two anxiolytics or two hypnotics in the first period vs. 23% in the second. The absence of withdrawal during hospitalisation was related to the high age and a diagnosis of depression rather than schizophrenia, to the existence of continuous intake over the 3 months preceding hospitalisation and to higher drug doses during the 7 days preceding hospitalisation. Prescription of treatment at the end of hospitalisation in previously non-user subjects was related to a higher HAD anxiety score at discharge.

Anxiolytic and hypnotic use by general hospital inpatients. The impact of psychopathology and general medical conditions.

This study explored the relative impact of general medical conditions and psychopathology on the current and lifetime use of anxiolytic and/or hypnotic drugs by general hospital inpatients. One hundred and five consecutive patients, admitted to an internal medicine department, were assessed by a structured interview about current and lifetime use of anxiolytic and/or hypnotic drugs, and with somatic and psychopathology scales. Eighty percent of patients reported using anxiolytics and/or hypnotics at least once in a lifetime, 62.9% in the last year, 55.2% in the last 3 months, and 42.9% in the last week. Correlations were found between drug use and current levels of anxiety and depression, but not somatic pathology. Psychological suffering appeared to be a major determinant for anxiolytic and/or hypnotic use by patients with general medical conditions. Consumption rates were higher than in the general population, but there was no direct link between somatic morbidity and drug use.

Anxiety, depression, psychotropic drug use and cognitive impairment.

BACKGROUND: Numerous studies have shown that anxiety and depression are related to cognitive impairment, but the concomitant association between anxious symptoms, depressive symptoms and cognitive function has not been investigated, and, most studies have not considered psychotropic drug use as a possible confounding factor. METHODS: We assessed the independent association between depression, anxiety, psychotropic drug use and cognitive performance in 457 men and 659 women, aged 59-71 years living in the community. Data on demographic background, occupation, medical history, drug use and personal habits were obtained using a standardized questionnaire. The Spielberger Inventory Trait and the Center for Epidemiologic Study-Depression (CES-D) scales were used to evaluate anxious and depressive symptomatology respectively. Cognitive assessment included six traditional tests covering the main areas of cognitive functioning. RESULTS: In men, anxious and depressive symptomatologies had independent significant associations with most cognitive abilities, independent of psychotropic drug use. In women, the association between anxiety or depression and cognitive functioning was less strong and disappeared after adjustment for psychotropic drug use. Psychotropic drug use was associated with lower cognitive scores in both sexes. In men with high CES-D scores, we found positive correlations between anxiety level and cognitive scores. CONCLUSIONS: The study showed that anxiety, depression and psychotropic drug use were significantly and independently associated with cognitive functioning in elderly men. The high prevalence of psychotropic drug use in women with or without psychological disorders may explain its major effect in women. Results suggested that anxiety may partly compensate for some negative effects of depression on cognitive functioning.

Anxiety but not depression is associated with elevated blood pressure in a community group of French elderly.

OBJECTIVE: This study examined whether anxiety and depression were independently associated with elevated blood pressure in elderly persons. METHOD: The study group consisted of 1389 subjects aged 59 to 71 years recruited from the electoral rolls of the city of Nantes (France). Subjects completed the Center for Epidemiologic Studies-Depression scale (CES-D) and the Spielberger Inventory scales to assess depressive symptoms and anxiety symptoms, respectively. Data were collected on sociodemographic characteristics, smoking and drinking habits, medical history, and drug use. Two measures of systolic and diastolic blood pressure were taken after a 10-minute rest. Body mass index was computed from weight and height measurements. Subjects taking antihypertensive drugs (N = 281) were excluded from the present analysis. RESULTS: Depression and anxiety scores were significantly correlated (r = .61 in men; r = .65 in women; p<.001). In univariate analyses, anxiety scores were correlated with systolic and diastolic blood pressure in men, but not in women; blood pressure was not associated with depressive symptoms in either sex. Multivariate logistic regressions, controlling for possible confounders, showed that in both men and women, the risk of high blood pressure increased with increasing anxiety scores; odds ratios for high blood pressure were less than 1 in subjects with depressive symptomatology. CONCLUSIONS: This study suggested that anxiety but not depression was independently associated with an increased risk for high blood pressure.

Prevalence and recognition of anxiety syndromes in five European primary care settings. A report from the WHO study on Psychological Problems in General Health Care.

BACKGROUND: This study explored the prevalence, socio-demographic characteristics and severity of different anxiety syndromes in five European primary care settings, as well as medical help-seeking, recognition by general practitioners (GPs) and treatment prescribed. METHOD: The data were collected as part of the WHO study on Psychological Problems in General Health Care. Among 9714 consecutive primary care patients, 1973 were interviewed using the Composite International Diagnostic Interview. Reason for contact, ICD-10 diagnoses, severity and disability were assessed. Recognition rates and treatment prescribed were obtained from the GPs. RESULTS: Anxiety syndromes, whether corresponding to well-defined disorders or to subthreshold conditions, are frequent in primary care and are associated with a clinically significant degree of severity and substantial psychosocial disability. Their recognition by GPs as well as the proportion treated are low. CONCLUSIONS: Since people with subthreshold anxiety show a substantial degree of disability and suffering, GPs may consider diagnostic criteria to be insufficient. However, their awareness of specific definitions and treatment patterns for anxiety disorders still needs a lot of improvement both for patients' well-being and for the cost resulting from non-treatment.

[Psychotropic drugs, anxiety and depression in the elderly population. The EVA study]. / Médicaments psychotropes, anxiété et dépression dans une population âgée. Etude EVA.

BACKGROUND: Prevalence of psychotropic drugs use increases with age, while that of depressive or anxiety disorders remains stable. The aim of this study was to define risk factors of psychotrope use in individuals aged 60 to 70 years. METHODS: We studied a sample of 1389 individuals recruited from the electoral rolls of the city of Nantes (EVA study). Data on sociodemographic characteristics, tobacco and alcohol use, presence of any chronic disease and drug use were collected. Depressive symptoms were assessed by the Center for Epidemiologic Studies-Depression scale and anxiety symptoms by the Spielberger Inventory scale. RESULTS: Fourteen per cent of men and 27% of women took at least one psychotropic drug. Multivariate logistic regression showed that psychotrope use was significantly associated with symptoms of anxiety or depression, in both men (odds-ratio = 3.9 [1.8-8.5]) and women (odds ratio = 4.0 [2.5-6.5]). The presence of chronic disease was not a risk factor for psychotrope use, particularly in men (odds ratio = 0.6 [0.3-1.3]). In both sexes, a high socio-economic level decreased the risk of psychotrope use. CONCLUSIONS: The present study does not confirm the role of chronic disease as a major risk factor for psychotropic drug use in elderly. The interpretation of the association between psychotrope use and symptoms of anxiety or depression is limited by several factors, in particular the absence of categorical psychiatric diagnosis and the cross-sectional nature of our data.

Clinical and economic comparison of sertraline and fluoxetine in the treatment of depression. A 6-month double-blind study in a primary-care setting in France.

In a double-blind study in a primary-care setting in France, outpatients fulfilling DSM IV criteria for a major depressive episode were randomised to receive sertraline (50 to 150 mg/day; n = 122) or fluoxetine (20 to 60 mg/day; n = 120). Assessments, including clinical evaluation [Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI)] and quality of life [Functional Status Questionnaire (FSQ)], were made at study entry and after 4 and 6 months of treatment. Use of medical services, absences from work and productivity losses were recorded for calculation of direct and indirect costs from both the overall societal perspective and in terms of sickness insurance. In total, 231 patients (116 receiving sertraline, 115 receiving fluoxetine) were included in an intention-to-treat analysis assessed up to the last visit. Statistically significant clinical and quality-of-life improvements from baseline were observed in both treatment groups, with no between-group differences. Utilisation of medical resources was higher in fluoxetine-treated patients, with significantly more consultations with specialists. The 2 treatment groups were similar in terms of number of hospitalisations and duration of stay, whether related to depression or not. There were no significant differences between groups for work or productivity losses. Cost comparisons favoured sertraline treatment from both the societal (FF7780 vs FF8706) and sickness insurance (FF2936 vs FF3224) viewpoints, with cost differentials of FF926 and FF288, respectively. From the societal perspective, the total cost per patient over the 6-month course of the trial, irrespective of the study treatment given, was FF8241, and the corresponding sickness insurance cost was FF3079. At the time of the study, FF1 = $US0.1993.

Phobic symptoms, particularly the fear of blood and injury, are associated with poor glycemic control in type I diabetic adults.

OBJECTIVE: To investigate the presence of psychiatric disorders and symptoms in type I diabetic patients and to identify those that may influence metabolic control as assessed by GHb levels. RESEARCH DESIGN AND METHODS: This was a cross-sectional study. One hundred and two consecutive patients with type I diabetes who were regular outpatient visitors of a diabetology department were evaluated. The psychiatric assessments included self-rating questionnaires (General Health Questionnaire and Fear Questionnaire) and observer-rating questionnaires (Montgomery-Asberg Depression Rating Scale [MADRS] and Mini International Interview). Diabetic characteristics were assessed by a structured interview. The observer was blind to the diabetic characteristics of the patients. RESULTS: Type I diabetic patients with GHb levels > or = 8% had higher psychological distress, scored significantly higher for symptoms of agoraphobia and for fear of blood and injury, had substantially higher levels of anxiety-depression, and performed significantly fewer blood glucose measurements per day. They did not differ in MADRS score from patients with GHb levels < 8%. Multivariate analysis showed that GHb was positively associated with the total score of phobic symptoms and the level of anxiety-depression and inversely associated with the number of daily blood glucose measurements. These factors explained 41% of the variance of GHb. The inverse relationship between GHb and the number of blood glucose measurements per day was mainly influenced by the fear of blood and injury. Patients with high scores for the fear of blood and injury performed fewer blood glucose measurements and had poorer glycemic control; conversely, subjects without fear of blood and injury performed more daily blood glucose measurements and had better glycemic control. CONCLUSIONS: Phobic symptoms are frequent in patients with type I diabetes. The intensity of phobic symptoms and anxiety-depression negatively influences metabolic control. Increased fear of blood and injury may lead some patients to perform few home blood glucose measurements and may result in poorer glycemic control. This suggests that, by decreasing the fear of blood, injury, and injection, metabolic control may be improved.

Pharmacologic treatment of obsessive-compulsive disorder: comparative studies.

The predominant hypothesis about obsessive-compulsive disorder (OCD) pathophysiology implicates abnormal serotonergic function regulation. Pharmacologic agents with potent serotonin reuptake-inhibiting properties have demonstrated effectiveness in treating OCD. In short-term clinical trials compared by meta-analysis, clomipramine and serotonin selective reuptake inhibitors (SSRIs) were found superior to placebo in improving symptoms of OCD. In one-to-one comparative studies, clomipramine has been found as efficacious as fluoxetine and fluvoxamine, and in a comparative trial of clomipramine with sertraline, there was a statistically superior response to sertraline after 16 weeks of treatment; moreover, discontinuation rate in patients taking clomipramine was more than twice that in patients taking sertraline (26% vs. 11%). In contrast to patients receiving clomipramine who showed poor tolerance in long-term use, patients maintained on fluoxetine for 24 weeks after an acute phase well tolerated the medication. In another study, patients responding to 12 weeks of sertraline treatment also showed improved tolerance during an additional 40-week period, with 75% completing the continuation phase. With long-term or even lifelong treatment appearing necessary for people with OCD, those agents that result in better tolerance will prove preferable.

[Insulin-dependent diabetes and psychiatric pathology: general clinical and epidemiologic review]. / Diabète insulino-dépendant et pathologie psychiatrique: revue générale clinique et épidémiologique.

Insulin dependent diabetes mellitus is one of the most common metabolic diseases and affects 150,000 persons in France. To achieve good metabolic control requires a strict daily management of the treatment by the patients themselves. Lack of active involvement can have direct consequences which underlines the importance of a good adherence to the treatment. About 50% of the patients do not obtain adequate metabolic control. The major problem of insulin treatment consists in the repeated occurrence of severe hypoglycemias which may be accompanied by an alteration of the perception of hypoglycaemic signs. On the other hand, when the risk of severe hypoglycaemia is removed, glycosylated haemoglobin levels rise. Permanent hyperglycaemia leads to numerous somatical complications. An extremely dramatic combination of these two types of metabolic unbalance is represented by the brittle diabetes characterised by very frequent and extreme oscillations between hypo and hyperglycaemia. This raises the question of the influence of psychopathological factors on metabolic control and the possibility of improving metabolic control by acting on these factors. Epidemiological studies in diabetic patients have established higher prevalence rates of psychiatric disorders, in particular mood and anxiety disorders. The current prevalence rate of depression was found to be homogeneous in the literature about 11% and life time prevalence rates of major depressive disorders vary between 24% and 29%. The symptom profile of depression in diabetic patients is similar to that in depressed non diabetic psychiatric patients and it has been shown that highly sensitive psychiatric diagnosis of depression can be made among diabetic patients. There is no specific personality pattern in diabetic patients. There seems to be a relationship between metabolic control as defined by glycosylated haemoglobin and psychiatric disorders. Indeed, high levels of glycosylated haemoglobin are found in patients with psychiatric disorders. There seems to be some evidence of an association between blood glucose levels and actual emotional states. Nothing is known about the specificity of the link between psychiatric disorders and insulin-dependent diabetes mellitus. No study has evaluated if the relationship between psychiatric disorders and insulin-dependent diabetes mellitus is due to the disease itself or to the chronic feature of diabetes.

Social phobia in primary care: level of recognition and drug use.

A study was conducted in Paris among primary care physicians as part of a World Health Organization study entitled Psychological Problems in General Health Care. Though social phobia is associated with significant impairment and drug use, the level of problem recognition by general practitioners was low. Social phobia (n = 38) was identified as a psychological case in 53% of the patients in whom social phobia was not comorbid with depression, and in 66% when comorbid with depression. This low level of recognition was comparable to that observed for depression where only 66% of the depressed patients (n = 121) were recognized as psychological cases. Psychotropic drug use was high: 61% of patients with social phobia had taken at least one psychotropic drug in the last month, compared to only 32% of those without social phobia. This difference was explained by a significant difference in the use of anxiolytics (45.4 versus 12.1%). The use of psychotropic drugs was twice as frequent in patients with social phobia who were depressed than in those not depressed. The results of this study emphasize the crucial need for primary care physician training in the recognition and treatment of mental disorders.

[Epidemiology of the use of anxiolytic and hypnotic drugs in France and in the world]. / Epidémiologie de la consommation des anxiolytiques et des hypnotiques en France et dans le monde.

A higher anxiolytic and hypnotic consumption has been evidenced in France by recent international and national surveys. In an effort to counteract this pattern French Health authorities have enforced limitation to the prescription of these drugs. Understanding the causes of this overuse needs a careful analysis of the pattern of use of this medicine but also of the associated morbidity factors. In the last ten years several studies have attempted to address these issues. In the general population there were 25 to 30% of occasional or regular users with between 5 and 7% chronic users making french anxiolytic users two to three time superior to most industrialised countries. This high level of consumption is not the privilege of anxiolytic since the same pattern of use is observed for all medicine. Studies in primary care, in medical inpatients and psychiatric inpatients show as expected that anxiolytic use increase with the psychiatric morbidity and also with somatic disorder. The main risk factors for anxiolytic use are female sex, old age and psychic and somatic morbidity. Age seems to play a major role in subjects over 65: 17% are chronic users. Multiple factors might play a role in benzodiazepine use as medical care system, physician type of practice, cultural specific aspects but no proper simple explanation is available to explain the mechanism of the french high anxiolytic use. Given the poor global recognition of mental disorder observed in most countries it is suggested to privilege primary care physician training in psychiatry to optimize psychotropic drug use.

Social phobia in general health care: an unrecognised undertreated disabling disorder.

BACKGROUND: This study explored the prevalence of social phobia (SP) in general health care, sociodemographic characteristics of patients with SP, the age at onset and severity of SP, its comorbidity with other psychiatric disorders, and the recognition by general practitioners. METHOD: The study was conducted in Paris as part of the WHO study on Psychological Problems in General Health Care. Among 2096 consecutive primary care patients, 405 were interviewed using the CIDI. DSM-III-R diagnoses, severity and disability were assessed. RESULTS: The one-month prevalence of SP is high (4.9) in primary care, although underdiagnosed by GPs. It has an early onset and leads to substantial disability. Patients with SP are at risk of developing further depression, alcoholism or suicidal behaviour. CONCLUSION: SP appears to be a true and frequently severe pathological condition. The awareness of GPs and the general population should be improved.

[Dependence on benzodiazepines. Clinical and biological aspects]. / Dépendance aux benzodiazépines. Aspects cliniques et biologiques.

The high rate of benzodiazepines (BZD) consumption has been repeatedly confirmed by epidemiological surveys in most major western world countries. In a recent french survey 7% of chronic users of BZD (use in 5/7 days for the last 12 months) were found the general population (17% in the population aged above 65). It has been suggested that the high BZD consumption rate could be related to dependence. The existence of BZD dependence was described in the early sixties with very high dose of chlordiazepoxide but it has become a real concern for the medical community since the late seventies with increasing number of reports of withdrawal symptoms. The extend of the actual rate of withdrawal symptoms at BZD tapering is still very controversial and according to the different studies it varies from 39 to 90%. The between studies difference in parameters such as: the patient populations (psychopathology, treatment duration), the type of tapering employed (duration, nature of the medical and psychological support) and the used operational criteria for withdrawal definition most likely explain this wide variation in the rate of occurrence of withdrawal manifestations. According to the American Psychiatric Association Task Force on Benzodiazepine Dependence, Toxicity and Abuse three type of pathological events can happen after treatment discontinuation: rebound, withdrawal syndrome and recurrence. The rebound consists in the early and transitory reappearance of the anxiety symptoms pre-existing to the treatment but in an exacerbated from; the withdrawal syndrome associates the resurgence of the pre-existing anxiety symptoms and new symptoms as sensory disturbances (metallic taste, hyperosmia, cutaneous exacerbated sensitivity, photophobia...) nausea, headache, motor disturbance in some rare cases depersonalization, paranoid reaction, confusion, convulsion. Rebound or withdrawal syndrome appearance delay varies from hours to few days according mostly to compounds elimination half-life. The relapse develops later with a progressive reapparance of pre-treatment symptoms. In practice recurrence and rebound are often difficult to isolate: recurrence can follow rebound. Different operational criteria of definition for this different entities have been proposed but there is a need for a consensual position. The treatment length, a high daily dose, an alcohol abuse history, a dependent personality and the severity of the psychopathology of the patients have been found to be predictive for the occurrence of withdrawal symptoms. Behavioural therapies (individual or in group) have been proposed with some success for the treatment of benzodiazepine dependence; drug treatment with carbamazepine or imipramine have demonstrated some efficacy. Other drug as buspirone clonidine having anxiolytic properties have not demonstrated efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)