Rita Schmid

Lithium’s Emerging Role in the Treatment of Refractory Major Depressive Episodes: Augmentation of Antidepressants

Background: The late onset of therapeutic response and a relatively large proportion of nonresponders to antidepressants remain major concerns in clinical practice. Therefore, there is a critical need for effective medication strategies that augment treatment with antidepressants. Methods: To review the available evidence on the use of lithium as an augmentation strategy to treat depressive episodes. Results: More than 30 open-label studies and 10 placebo-controlled double-blind trials have demonstrated substantial efficacy of lithium augmentation in the acute treatment of depressive episodes. Most of these studies were performed in unipolar depression and included all major classes of antidepressants, however mostly tricyclics. A meta-analysis including 10 randomized placebo-controlled trials has provided evidence that lithium augmentation has a statistically significant effect on the response rate compared to placebo with an odds ratio of 3.11, which corresponds to a number-needed-to-treat of 5. The meta-analysis revealed a mean response rate of 41.2% in the lithium group and 14.4% in the placebo group. One placebo-controlled trial in the continuation treatment phase showed that responders to acute-phase lithium augmentation should be maintained on the lithium-antidepressant combination for at least 12 months to prevent early relapses. Preliminary studies to assess genetic influences on response probability to lithium augmentation have suggested a predictive role of the –50T/C single nucleotide polymorphism of the GSK3β gene. Conclusion: Augmentation of antidepressants with lithium is currently the best-evidenced augmentation therapy in the treatment of depressed patients who do not respond to antidepressants.

Predicting inpatient suicides and suicide attempts by using clinical routine data

OBJECTIVE The study aimed at exploring prevalence and risk factors of inpatient suicides and attempted suicides in a psychiatric hospital. METHOD Based on the German psychiatric basic documentation system, 20,543 patients with 40,451 episodes of inpatient care (1995-2004) in a psychiatric state hospital were included. Besides univariate analyses, multivariate logistic regression analyses and classification and regression tree analyses were performed. RESULTS Forty-one inpatient suicides were recorded. Risk of inpatient suicide is increased for patients with resistance to psychopharmacological treatment, previous suicide attempt, severe side effects and supportive psychotherapy before admission. Two hundred fourteen inpatient suicide attempts occurred during the 10-year period. Risk factors of inpatient suicide attempt are assault, personality disorder, previous suicide attempt, psychopharmacological treatment resistance, suicidal thoughts at admission, schizophrenia, depression, female sex and length of stay. CONCLUSION The identified risk factors underline the need for a cautious investigation of previous suicide attempts as well as for giving special attention to patients who have problems with psychopharmacotherapy during hospitalization.

Subsyndromal Mood Symptoms: A Useful Concept for Maintenance Studies of Bipolar Disorder?

Objective: To explore the measurement of subsyndromal mood symptoms in relation to studies of maintenance therapy for bipolar disorder. Methods: Literature review of the Medline database using the following selection criteria: (1) ‘bipolar disorder’ plus ‘inter-episode or interepisode or subsyndromal or subclinical or residual or subthreshold’ and (2) ‘bipolar disorder’ plus ‘maintenance or prophylaxis or longitudinal’. Studies of children or adolescents and non-English-language reports were excluded. Results: Of the studies published between 1987 and October 2007, 77 articles about subsyndromal mood symptoms and 257 studies of maintenance therapy agents were found. Only 11 of the 257 studies of maintenance therapy agents discussed subsyndromal mood symptoms. Of the 77 articles, two thirds were published after 2000. Inconsistent definitions of subsyndromal mood symptoms and different evaluation tools and methodologies were used in the studies. Conclusions: There is a need to standardize definitions and validate measuring approaches for subsyndromal mood symptoms. However, when measured in both naturalistic studies and clinical trials, subsyndromal mood symptoms were frequently reported by patients receiving maintenance therapy and were associated with poor functioning. As with other chronic illnesses, knowledge of the patient’s perspective of daily morbidity is important for improving the clinical outcome. Studies of maintenance therapy for bipolar disorder, regardless of the approach, should measure subsyndromal mood symptoms as an additional outcome.

Association between age of onset and mood in bipolar disorder: comparison of subgroups identified by cluster analysis and clinical observation.

BACKGROUND This study compared subgroups identified by cluster analysis and clinical observation by evaluating the association between the age of onset of bipolar disorder and self-reported daily mood ratings. METHODS Two hundred and seventy patients with bipolar disorder provided daily self-reported mood ratings for about 6 months returning 55,188 days of data. The age of onset subgroups were determined both using previously defined cutoff values based upon clinical observation (≤12 years, 13-19 years, 20-29 years, >29 years), and model-based cluster analysis. Demographic characteristics were compared in the age of onset subgroups. Univariate general linear models with age of onset subgroups and other demographic variables as fixed factors and covariates were used to analyze the percent of days depressed, euthymic and hypomanic/manic. RESULTS Using the predetermined subgroups, demographic differences were found between the four subgroups in the diagnosis of bipolar I/II, years of illness, age and use of lamotrigine. Post-hoc pairwise comparison found that patients with an age of onset less ≤ 12 years spent more days hypomanic/manic: 16.4 percent versus 8.0 for patients with an age of onset between 13 and 19 years (p=0.006) and 8.2 percent for patients with an age of onset between 20 and 29 years (p = 0.031). The majority of the additional days of hypomania/mania occurred outside of an episode. Model-based cluster analysis found a mixture of 2 distributions of onset with peaks at age 15.1 years (SD = 4.7) and 27.5 years (SD = 10.2). Analysis of these two subgroups detected no significant differences in demographic characteristics or mood ratings. CONCLUSION Age of onset subgroups arising from clinical observation may be more useful than those determined by cluster analysis.

Comparison of sleep/wake parameters for self-monitoring bipolar disorder

BACKGROUND Psychosocial interventions may teach patients with bipolar disorder to successfully detect warning signs of relapse. These interventions often include ongoing self-monitoring of sleep. We previously reported that a change in sleep duration (sleep plus bedrest) of >3 h may indicate that a mood change is imminent. This analysis further investigated whether sleep duration, sleep onset or sleep offset was the most useful sleep/wake parameter to monitor for an oncoming mood change. METHODS 101 adult outpatients receiving treatment as usual recorded mood, sleep and medications every day on a home computer for a mean of 265+/-103 days. A daily time series of mood, sleep duration (sleep plus bedrest), sleep onset and sleep offset was constructed for each patient. After applying an ARIMA (0,1,1) filter, a cross correlation function was used to analyze the temporal relationship between the residuals for lags of +/-7 days. RESULTS Less frequent significant correlations were found between a change in either sleep onset or sleep offset and mood, than between sleep duration and mood. Patients with a significant correlation between sleep duration and mood included 86% of those with a significant correlation between sleep onset or sleep offset and mood. Mean sleep duration when euthymic was long (> or =8 h in 89% of patients, > or =9 h in 51% of patients). LIMITATIONS Self-reported data, naturalistic study, and computer access required. CONCLUSIONS Self-monitoring of sleep duration is recommended for patients with bipolar disorder. Better understanding of the long sleep duration of euthymic patients is required.

The association between concurrent psychotropic medications and self-reported adherence with taking a mood stabilizer in bipolar disorder

Multiple psychotropic medications are routinely prescribed to treat bipolar disorder, creating complex medication regimens. This study investigated whether the daily number of psychotropic medications or the daily number of pills were associated with self‐reported adherence with taking a mood stabilizer.

The forgotten caregivers: Siblings of schizophrenic patients

Objective. The situation of caregivers of psychiatric patients is mostly focussed on burdens of parents or spouses of patients. The burden of siblings due to the illness, however, is mostly underestimated and disregarded. Methods. Thirty-seven narrative interviews with siblings of schizophrenia inpatients were analysed by using a summarizing content analysis. The founded global statements were quantitatively analysed. Regression-analysis as well as regression trees were used to evaluate the data linked with sociodemographic and disease-related variables of the patient and siblings. Results. The results showed a high proportion of siblings engaged in caregiving activities. A total of 492 individual statements were summarized in 26 global types of statements. The three most often reported burdens by the healthy siblings are: “Handling the symptoms of illness” (100%), “Emotional burden due to the illness of the sibling” (100%) and “Uncertainty in judging what amount of stress the patient can cope with” (81.1%). Linear regression and regression tree analysis show predictors for higher burdened siblings. Conclusion. Siblings of schizophrenia patients are burdened in various aspects and in a specific matter. Their special needs will therefore have to be recognised before they can receive appropriate intervention.

Suicidal Behaviour of Elderly Psychiatric Inpatients - Prevalence and Risk Factors

OBJECTIVE The study aimed at evaluating prevalence and risk factors of suicidal behaviour of elderly psychiatric inpatients based on the German psychiatric basic documentation system (DGPPN-BADO). METHODS A total of 5,356 elderly psychiatric inpatients (> 65 years) with 7,658 episodes of inpatient care in a psychiatric university hospital between 1996 and 2006 was included in the study. Besides descriptive analyses, univariate analyses and binary logistic regression analyses were performed. RESULTS Four inpatient suicides and 14 attempted suicides of twelve inpatients were recorded during the 11-year period. Three of the 4 inpatient suicides and 6 of the 12 inpatients attempting suicide during hospital stay had a diagnosis of depression. Furthermore, 280 suicides before admission were attempted by 262 patients. Regression analysis revealed life time suicide attempt, ICD-10 diagnosis F43, period of onset of present episode less than one week and ICD-10 diagnosis F32 / F33 as significant predictors of attempted suicide before admission. Suicidal thoughts without concomitant suicide attempt before admission were recorded for 389 admissions of 346 patients. According to regression analysis, risk of suicidal thoughts before admission is increased for patients with life time suicide attempt, ICD-10 diagnosis F43, ICD-10 diagnosis F32 / F33, ICD-10 diagnosis F30 / F31, greater number of hospital admissions, short cumulative length of stay and non-chronic course of disease. CONCLUSIONS Examination of risk faktors of suicidal behaviour within the framework of hospital admissions should not be restricted exclusively to period of hospital stay. Relevant risk factors can be found even before hospital stay and could be a cue for suicide prevention already in the forefront of admission.

Risk Profiles for Suicide of Schizophrenic and Depressive Inpatients - A Psychological Autopsy Study

OBJECTIVE This psychological autopsy study investigates suicide risk factors of schizophrenic and depressive inpatients. METHODS 67 potential risk factors of inpatient suicide were identified by means of literature research and caregiver interviews of schizophrenic and depressive suicidents (1995-2004). The medical records of the suicidents (n = 20) were analysed in respect to the identified risk factors and compared to their respective control group of non-suicidents (n = 20) which was matched by diagnosis, gender, age, year / month of admission and ward. Univariate and multivariate statistical analyses were performed. RESULTS In comparison to their respective control group schizophrenic (n = 11) and depressive suicidents (n = 9) differed clearly by their risk profile. Suffering from side effects of medication was found to be a predictor of suicide for schizophrenic inpatients. CONCLUSIONS Psychological autopsy studies are indispensable for the construction of diagnosis-specific risk profiles. Reduction of side effects of medication seems to play a larger role in suicide prevention for schizophrenic inpatients than previously assumed.

Association between median family income and self-reported mood symptoms in bipolar disorder

OBJECTIVE There is broad consensus from epidemiologic research that lower socioeconomic status is related to poorer health. This study investigated the relation between median family income and self-reported mood symptoms in patients with bipolar disorder who reside in the United States. METHODS Two hundred eighty-four patients with bipolar disorder provided daily self-reported mood ratings for 6 months (50,054 days of data). Regardless of income, all patients were treated by a psychiatrist, took psychotropic medications, and participated in computerized self-monitoring throughout the study. Median family income was obtained from US census tract data. The association between income and mood was analyzed using income as both a continuous and categorical variable. Demographic characteristics were compared by income group. Education level was included in the analysis a priori. RESULTS Both the continuous and categorical approaches found a positive association between income and euthymia, a negative association between income and manic/hypomanic symptoms including those due to mixed states, and no association between income and depressive symptoms. Patients in the lower-income group spent 12.4% fewer days euthymic than those in the upper-income group and 9.7% fewer days euthymic than those in the middle-income group. Patients in the lower-income group spent 7.1% more days with manic/hypomanic symptoms than those in the upper-income group. There was no association between education and income. CONCLUSION Median family income is associated with mood symptoms in patients with bipolar disorder. Inclusion of income as a measure of socioeconomic status is recommended for future studies of outcome in bipolar disorder.