The onset of action of antidepressants often takes 4 to 6 weeks. The antidepressant effect of wake therapy (sleep deprivation) comes within hours but carries a risk of relapse. The objective of this study was to investigate whether a new chronotherapeutic intervention combining wake therapy with bright light therapy and sleep time stabilization could induce a rapid and sustained augmentation of response and remission in major depressive disorder.
75 adult patients with DSM-IV major depressive disorder, recruited from psychiatric wards, psychiatric specialist practices, or general medical practices between September 2005 and August 2008, were randomly assigned to a 9-week chronotherapeutic intervention using wake therapy, bright light therapy, and sleep time stabilization (n = 37) or a 9-week intervention using daily exercise (n = 38). Patients were evaluated at a psychiatric research unit. The study period had a 1-week run-in phase in which all patients began treatment with duloxetine. This phase was followed by a 1-week intervention phase in which patients in the wake therapy group did 3 wake therapies in combination with daily morning light therapy and sleep time stabilization and patients in the exercise group began daily exercise. This phase was followed by a 7-week continuation phase with daily light therapy and sleep time stabilization or daily exercise. The 17-item Hamilton Depression Rating Scale was the primary outcome measure, and the assessors were blinded to patients' treatment allocation.
Both groups responded well to treatment. Patients in the wake therapy group did, however, have immediate and clinically significantly better response and remission compared to the exercise group. Thus, immediately after the intervention phase (week 2), response was obtained in 41.4% of wake therapy patients versus 12.8% of exercise patients (odds ratio [OR] = 4.8; 95% CI, 1.7-13.4; P = .003), and remission was obtained in 23.9% of wake therapy patients versus 5.4% of exercise patients (OR = 5.5; 95% CI, 1.7-17.8; P = .004). These superior response and remission rates obtained by the wake therapy patients were sustained for the whole study period. At week 9, response was obtained in 71.4% of wake therapy patients versus 47.3% of exercise patients (OR = 2.8; 95% CI, 1.1-7.3; P = .04), and remission was obtained in 45.6% of wake therapy patients and 23.1% of exercise patients (OR = 2.8; 95% CI, 1.1-7.3, P = .04). All treatment elements were well tolerated.
Patients treated with wake therapy in combination with bright light therapy and sleep time stabilization had an augmented and sustained antidepressant response and remission compared to patients treated with exercise, who also had a clinically relevant antidepressant response.
Analysing duration of treatment episodes has become a standard task in many pharmacoepidemiological studies. However, such analyses are often carried out in a rather simplistic manner and more subtle issues are often ignored. In this paper, methods of analysing duration treatment episodes beyond simple analyses allowing investigation of the risk for certain events over time are demonstrated. In particular, the use of cumulative incidence functions, cause-specific hazard functions, hazard rate models and expected mortality in analysing duration of episodes is presented. We used these statistical techniques in analysing the early treatment history of patients who started a regular treatment with antidepressant drugs in the primary health care sector in Denmark. We have extracted some important features: The risk of discontinuing and switching treatment was very high around 10 weeks after starting treatment. After discontinuing the first treatment period, many patients soon started a second treatment period depending on the duration of the first treatment period with highest risk around 10 weeks. The mortality rate among the patients in treatment was about three times higher than the expected mortality. The risk of dying immediately after stopping treatment was about twice the expected mortality. The analysis suggests that: (1) there is a critical period for a first discontinuing, switching and restarting treatment around 10 weeks, (2) the GPs prescribing habits have more influence on the patterns than patient or drug characteristics, (3) over time Danish GPs tend to prolong the duration of first treatment period and avoid longer treatment breaks.
Studies have shown that lithium may cause psychomotor and cognitive impairment and impose an increased risk of traffic accidents. The antiepileptic drug valproate is also used as a mood stabilizer, but the impact on traffic safety has not been studied. The objective of the present study was to examine whether the use of lithium or valproate increased the risk of being involved in traffic accidents.
Between April 2004 and September 2006, information on prescriptions, road accidents and emigrations/deaths was obtained from three Norwegian population-based registries. Data on people between the ages 18-70 (3.1 million) were linked. Exposure consisted of receiving prescriptions for either lithium or valproate. Standardized incidence ratios (SIRs) were calculated by comparing the incidence of motor vehicle accidents during time exposed with the incidence over the time not exposed. Lithium was studied separately from valproate.
During the study period, 20,494 road accidents occurred including 36 while exposed to lithium and 31 while exposed to valproate. The overall accident risk was neither increased after having received prescriptions for lithium (SIR 1.3; 95%CI: 0.9-1.8), nor after having received a prescription for valproate (SIR 0.9; 0.6-1.3). The exception was a three-fold increase in risk for younger female drivers exposed to lithium.
We found no increase in the traffic accident risk after being exposed to lithium or valproate, except for young female drivers on lithium. This may be because these drugs carry no increased risk or because patients exposed to these drugs refrain from driving.
The Swedish Diagnosis and Therapy Survey was used to analyse the prescribing of antidepressants from 1991 to 1996. There were considerable differences in doses prescribed depending on diagnosis. Adequate dosage is an important factor in antidepressant treatment, and this study showed that tricyclic antidepressants are often prescribed at lower than recommended doses for the treatment of depression. Significantly higher doses were prescribed in continued treatment, as opposed to in new treatment, indicating dose titration when using tricyclic antidepressants and the most common selective serotonin reuptake inhibitors in depression. The findings from the present study suggest that the optimal dosage for some of the new antidepressants in clinical practice has not yet been determined and that costs of treatment in a natural setting might be considerably higher than costs calculated from dose recommendations.
Mindfulness-based cognitive therapy (MBCT) is a group-based psychosocial intervention designed to enhance self-management of prodromal symptoms associated with depressive relapse.
To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy, the current standard of care.
Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were randomized to receive maintenance antidepressant medication, MBCT, or placebo and were followed up for 18 months.
Outpatient clinics at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and St Joseph's Healthcare, Hamilton, Ontario.
One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes. Of these, 84 achieved remission (52.5%) and were assigned to 1 of the 3 study conditions.
Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT, continued taking their therapeutic dose of antidepressant medication, or discontinued active medication and were switched to placebo.
Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV.
Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in randomized patients (P = .03). Among unstable remitters (1 or more Hamilton Rating Scale for Depression score >7 during remission), patients in both MBCT and maintenance treatment showed a 73% decrease in hazard compared with placebo (P = .03), whereas for stable remitters (all Hamilton Rating Scale for Depression scores =7 during remission) there were no group differences in survival.
For depressed patients achieving stable or unstable clinical remission, MBCT offers protection against relapse/recurrence on a par with that of maintenance antidepressant pharmacotherapy. Our data also highlight the importance of maintaining at least 1 long-term active treatment in unstable remitters.
Cites: Arch Gen Psychiatry. 2004 Jan;61(1):34-4114706942
The aim of the study was to examine mortality risk associated with use of antidepressants and antipsychotics classified with torsades de pointes (TdP) risk in elderly.
A matched case-control register study was conducted in people 65 years and older dying outside hospital from 2008-2013 (n = 286,092) and matched controls (n = 1,430,460). The association between prescription of antidepressants and antipsychotics with various TdP risk according to CredibleMeds (www.crediblemeds.org) and all-cause mortality was studied by multivariate conditional logistic regression adjusted for comorbidity and several other confounders.
Use of antidepressants classified with known or possible TdP risk, was associated with higher adjusted risk for mortality (OR 1.53, 95% CI 1.51, 1.56 and OR 1.63, 95% CI 1.61, 1.67, respectively) compared with antidepressants classified with conditional TdP risk (OR 1.25, 95% CI 1.22, 1.28) or without TdP classification (OR 0.99, 95% CI 0.94, 1.05). Antipsychotics classified with known TdP risk were associated with higher risk (OR 4.57, 95% CI 4.37, 4.78) than antipsychotics with possible risk (OR 2.58, 95% CI 2.52, 2.64) or without TdP classification (OR 2.14, 95% CI 2.03, 2.65). The following risk ranking was observed for commonly used antidepressants: mirtazapine > citalopram > sertraline > amitriptyline and for antipsychotics: haloperidol > risperidone >olanzapine > quetiapine.
The CredibleMeds system predicted drug-associated risk for mortality in the elderly at the risk class level. Among antipsychotics, haloperidol, and among antidepressants, mirtazapine and citalopram, were associated with the highest risks. The results suggest that the TdP risk with antidepressants and antipsychotics should be taken into consideration when prescribing to the elderly.
To establish whether the young women (15-24 year old) who committed suicide in Sweden (1999-2013) received antidepressant treatment or not, and to what extent, prior to and/or at the time of suicide. To investigate the belief that increased prescription of antidepressants would drastically reduce the number of suicides.
An analysis of data from the Swedish Prescribed Drug Register, the Causes of Death Register, with registers cross checked, and from the National Board of Forensic Medicine.
This analysis shows a covariance between increased prescription of antidepressants and an increasing trend in the number of suicides among young women. In the period 1999-2003 antidepressants were found in toxicological analyses done in 23% of the young women who committed suicide, and in 39% of cases for 2009-2013.
An increasingly larger proportion of young women who later committed suicide, had in the last few years been treated with antidepressants, prior to and at the time of the suicide. The previous assumptions that treatment with antidepressants would lead to a drastic reduction in suicide rates, are incorrect for the population of young women. On the contrary, it was found that an increasing tendency of completed suicides follow the increased prescription of antidepressants.
OBJECTIVE: To elucidate potential problems concerning the use of antidepressants (AD) in general practice. DESIGN: Cross-sectional, descriptive interview study. SETTING: General practices, Odense, Denmark. SUBJECTS: Random sample consisting of 98 AD users from 12 general practices. MAIN OUTCOME MEASURES: Indication for AD treatment, justification of the treatment, duration of AD treatment, daily dose of AD, side effects, Hamilton depression rating, WONCA score. RESULTS: The primary indication for AD treatment was depression (72 patients), partly regular depression (therapeutic/prophylactic treatment) (n = 39), partly depressive tendencies (n = 32) (1 unknown). Median treatment duration was 3 years; 25% had been in treatment for more than 10 years. The general practitioners judged the treatment problematic/unacceptable in 23 cases, largely because of uncertain indication or because other or no treatment was considered better for the patient. The daily doses of AD were generally low. Side effects were modest. The patients often had a relatively high depression score and poor status according to the WONCA-scale. CONCLUSIONS: The use of low doses, long duration of treatment, and uncertainty about the relevance of the treatment are important features of the use of AD by general practitioners. There seems to be a discrepancy between the use of AD in general practice and the scientifically-based recommendations.