Позднее начало лечения депрессии ассоциировано с худшим ответом на терапию

Background

The duration of untreated illness has been considered a likely predictor of the course of psychotic disorders. However, there is only sparse data concerning the influence of treatment delay on the outcome of mood disorders. The present study aimed to assess the effect of prolonged untreated depression on the outcome of antidepressant treatment.

Method

Patients aged 18–70 years with recent onset of the first lifetime depressive episode were systematically recruited by the Danish Psychiatric Central Research Register during a 2-year period. A total number of 399 individuals out of 1006 potential participants in the Register were interviewed, and 270 fulfilled the inclusion criteria. The validity of the diagnosis, duration of untreated illness, remission on first-line antidepressant treatment and a number of covariates, including psychiatric co-morbidity, personality disorders and traits, stressful life events prior to onset, and family history of psychiatric illness, were assessed by structured interviews.

Results

The remission rate was significantly decreased among patients with six months or more of untreated depression as compared to patients who were treated with antidepressant medication earlier after onset (21.1% versus 33.7%, OR=0.5, 95% CI 0.3 to 0.9, p=0.03). The negative influence of a prolonged DUI on the outcome did not seem confounded by any of a wide range of demographic and clinical variables.

Limitations

The outcome was evaluated retrospectively. The findings cannot be generalized to patients outside hospital settings.

Conclusion

Initiation of antidepressant treatment more than six months after onset of first episode depression reduces the chance of obtaining remission. The results emphasize the importance of early recognition and treatment of patients suffering from depression.

The effect of prolonged duration of untreated depression on antidepressant treatment outcome

Ранние признаки шизофрении, длительность нелеченного психоза, предупреждение первого психоза

Early Antecedents and Detection of Schizophrenia

Риск обострения при отмене препаратов через год после первого эпизода и при противорецедивной терапии кветиапином

Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.

Interventions Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.

Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.

Results 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; χ2=3.20, df=1; P=0.07).

Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year.

Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial

Омега-3 ПНЖК в предупреждении развития психоза

Eighty-one putatively prodromal patients (16.4 years, 33.3% male) were included in this 12-month, randomized, double-blind, placebo-controlled trial comparing 1.2 g omega-3 PUFA (700 mg eicosapentaenoic acid [EPA] and 420 mg docosahexaenoic acid [DHEA]h) with placebo over 12 weeks with a follow-up of 40 weeks off medication/placebo. Randomization was stratified with regard to depressive symptoms (cut-off score on the Montgomery-Asberg Depression Rating Scale [MADRS]). Operationally defined conversion rates served as the outcome measure, with psychopathology ratings as secondary measures. Overall, this study had a very high 12-month completion rate (93.8%); adherence rates based on pill count and self-rating were as high as 81% and 75% in the active and placebo groups. The main result was that patients treated for 3 months with omega-3 PUFAs had significantly lower conversion rates to psychosis, at the end of the acute 3-month treatment phase and also after an additional 9 months off omega-3 PUFA (12-month conversion rate: 4.9% vs 27.5%). The number needed to treat (NNT) to prevent 1 additional patient with conversion to psychosis at 1 year was only 5. In addition, positive, negative, and general symptoms measured by the Positive and Negative Syndrome Scale (PANSS) were significantly more reduced in the active treatment group, whereas adverse events did not differ. Finally, the ratio of putatively beneficial omega-3 to omega-6 fatty acids increased significantly, linking the clinical effects to a proposed biological mechanism.

The Year in Psychosis and Bipolar Disorder: Omega-3s and Psychosis Prevention

Поддерживающая терапия в комбинации с психосоциальным вмешательством

Xiaofeng Guo, M.D., and Jinguo Zhai, M.D., and colleagues evaluated this combination of therapies in 1,268 patients with early-stage schizophrenia treated from 2005 to 2007. A total of 633 were randomly assigned to receive schizophrenia drugs plus a psychosocial intervention involving 48 one-hour group sessions.

The psychosocial intervention included four evidence-based practices: psychoeducation (instruction for families and caregivers about mental illness), family intervention (teaching coping and socializing skills), skills training and cognitive behavioral therapy.

The other 635 patients received medication alone.

Rates of treatment discontinuation or change were 32.8 percent in the combined treatment group, compared with 46.8 percent in the medication-only group. The risk of relapse was lower among patients in the combination group, occurring in 14.6 percent of patients in that group and 22.5 percent of patients in the medication-only group.

The combined treatment group also exhibited greater improvements in insight, social functioning, activities of daily living and on four domains of quality of life, and a significantly higher proportion of them were employed or received education. There were no significant differences in either frequency or type of adverse events between the groups.

Early Meds, Counseling Aid Schizophrenia

Индивидуальное дозирование антипсихотиков

Paralleling the preclinical evidence, are there clinical data to suggest antipsychotic tolerance with continuous treatment? Work with first-episode schizophrenia has confirmed three findings related to antipsychotic treatment: (a) response to lower doses; (b) sensitivity to side effects; and (c) comparatively high response rate.[2,21] In contrast, the more chronic stages of schizophrenia are associated with higher antipsychotic doses and diminished clinical response,[22,23] keeping in mind that the chronic population is more heterogeneous and includes a larger proportion of refractory patients who may be receiving higher doses. While antipsychotic tolerance has been raised to account for a progressive decline in response,[24] nonadherence and/or illness progression are routinely endorsed as more viable explanations. That as many as 25% of individuals on depot antipsychotic therapy relapse[25] tempers the nonadherence argument, but at the same time does not rule out alternative explanations, eg, a discrete breakthrough episode vs tolerance per se. In contrast, the preclinical description of behavioral dopamine supersensitivity closely parallels the notion of "supersensitivity psychosis" and withdrawal dyskinesias reported clinically, linked to D2 upregulation as a result of ongoing antipsychotic exposure and observed in the face of drug discontinuation.[26–28]

Antipsychotic Dosing: How Much but Also How Often?

Ведение пациентов с первым приступом психоза

ВЕДЕНИЕ ПАЦИЕНТОВ С ПЕРВЫМ ПРИСТУПОМ ПСИХОЗА

продром, длительность нелеченного психоза, первый психотический эпизод

Most patients presenting to health services with an 'at risk mental state' will not develop psychosis. In the original Yung and McGorry study, transition rates were 40% over 12 months, but more recent studies found rates more in the vicinity of 15-30%. This still represents a level of risk increased a thousand-fold over the general population...
These early trials raise the possibility of primary or at least secondary prevention of psychotic disorders, although many questions remain. There are ethical issues in treating a group of people of whom 80% will not in any case progress to psychosis in the short term. Also, the base-rates, specificity and sensitivity of these at risk mental states in predicting psychosis may still mean this approach is of limited value at a population level...
Recovery rates from the first episode are high, with 85% achieving remission over a mean time of 3 months. Individuals in the first episode are sensitive both to the therapeutic effects and the adverse effects of antipsychotic drugs. This means they are more likely to respond to lower doses than in later episodes, but also are more susceptible to motor side effects. Most expert opinion advocates second generation antipsychotics as first line treatment (e.g. initially 0.5-2 mg risperidone or 2.5-7.5 mg olanzapine per day). Benzodiazepines are often used as adjuncts for agitation or catatonic symptoms. Poor adherence with treatment is if anything more problematic than at later stages of illness, since placebo controlled trials show a greater benefit of antipsychotics in first episode treatment and first relapse prevention yet up to 50% of individuals will be non-adherent in the first year. Cognitive behaviour therapy in addition to drug treatment is indicated.

Early Detection of Schizophrenia: Post-Detection: Early Treatments in the First Episode