Objective
Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium ...responsiveness (LR) is predictable using clinical markers.
Method
Our data are the largest existing sample of direct interview‐based clinical data from lithium‐treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR—as defined by the previously validated Alda scale—against 180 clinical predictors.
Results
Under appropriate cross‐validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78–0.82) and a Cohen kappa of 0.46 (0.4–0.51). The model demonstrated a particularly low false‐positive rate (specificity 0.91 0.88–0.92). Features related to clinical course and the absence of rapid cycling appeared consistently informative.
Conclusion
Clinical data can inform out‐of‐sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between‐site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between‐ and within‐site heterogeneity, and further testing such models on new external datasets.
Objective: Evidence based on controlled studies is still limited for treatment strategies that prevent recurrence of suicide attempts. Findings from observational as well as meta‐analytic studies ...strongly suggest that lithium may have suicide‐protective properties.
Method: Patients with a recent suicide attempt in the context of an affective spectrum disorder (n = 167) were treated with either lithium or placebo during a 12‐month period.
Results: Survival analysis showed no significant difference of suicidal acts between lithium and placebo‐treated individuals (adjusted hazard ratio 0.517; 95% CI 0.18–1.43). However, post hoc analysis revealed that all completed suicides had occurred in the placebo group accounting for a significant difference in incidence rates (P = 0.049).
Conclusion: Results indicate that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with affective disorders. Our findings contribute to the growing body of evidence suggesting a specific antisuicidal effect of lithium.
Therapeutic Drug Monitoring (TDM) is a valid tool to optimise pharmacotherapy. It enables the clinician to adjust the dosage of drugs according to the characteristics of the individual patient. In ...psychiatry, TDM is an established procedure for lithium, some antidepressants and antipsychotics. In spite of its obvious advantages, however, the use of TDM in everyday clinical practice is far from optimal. The interdisciplinary TDM group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has therefore worked out consensus guidelines to assist psychiatrists and laboratories involved in psychotropic drug analysis to optimise the use of TDM of psychotropic drugs. Five research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration of 65 psychoactive drugs: (1) strongly recommended, (2) recommended, (3) useful, (4) probably useful and (5) not recommended. A second approach defined indications to use TDM, e. g. control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning the drug metabolism, children, adolescents and elderly patients. Indications for TDM are relevant for all drugs either with or without validated therapeutic ranges. When studies on therapeutic ranges are lacking, target ranges should be plasma concentrations that are normally observed at therapeutic doses of the drug. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed for those drugs, for which the evaluation of the literature demonstrated strong evidence. Moreover, situations are defined when pharmacogenetic (phenotyping or genotyping) tests are informative in addition to TDM. Finally, practical instructions are given how to use TDM. They consider preparation of TDM, analytical procedures, reporting and interpretation of results and the use of information for patient treatment. Using the consensus guideline will help to ensure optimal clinical benefit of TDM in psychiatry.
The management and treatment of patients with suicidal behavior is one of the most challenging tasks for health-care professionals. Patients with affective disorders are at high risk for suicidal ...behavior, therefore, should be a target for prevention. Numerous international studies of lithium use have documented anti-suicidal effects since the 1970s. Despite the unambiguous evidence of lithium’s anti-suicidal effects and recommendations in national and international guidelines for its use in acute and maintenance therapy of affective disorders, the use of lithium is still underrepresented. The following article provides a comprehensive review of studies investigating the anti-suicidal effect of lithium in patients with affective disorders.
Objective: Studies on the time sense of depressed patients have revealed inconsistent results. Manic patients have been almost neglected.
Method: Patients with a major depressive episode (n = 32), ...or a manic episode (n = 30) (both Diagnostic and Statistical Manual of Mental Disorders‐IV, Mini‐International Neuropsychiatric Interview‐confirmed), and 31 healthy controls were included. The subjective time experience was assessed by a visual analog scale (VAS), the objectively measurable time judgment abilities by the Chronotest, a computer program developed for this study, consisting of time estimation and time production tasks.
Results: Controls reported a balanced, manic patients an enhanced, and depressive patients a slowed experience of time flow in the VAS (P < 0.001). In the time judgment tasks, however, both depressed and manic patients showed time overestimation for the longer time spans (P < 0.008).
Conclusion: This largest study on time sense in manic patients confirmed results of a divergent alteration of time experience in depressive and in manic patients but revealed an uniform time overestimation by both patient groups in time judgment tasks.
Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with ...greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (AkdÄ) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range.
The spontaneous reporting system (srs) is the most important early warning system of adverse drug reactions. As there is serious under-reporting we studied the respective knowledge and attitudes of ...two samples of physicians in Germany. Five hundred randomly sampled physicians and 815 physicians who had actually reported an ADR were included; the response rate to the mail questionnaire was 51.4 and 43.9%, respectively; 61.3% said to have reported at least one case in their life. As many as 75–85% of physicians said never to have sent an ADR report to the governmental or professional reporting systems. Reporting to pharmaceutical companies, on the other hand, has been substantially better. Sixty-eight and two-tenths percent indicated to have suspected an ADR without reporting it. Major reasons for not reporting were: ADR well known (75.6%), too trivial (71.1%), causality uncertain (66.3%). The ADR with the highest probability of being reported were serious unknown adverse reactions of a new drug (81.1%) or an established drug (72.9%) and serious known reactions to a new drug (65.2%). Almost 20% of the physicians admitted to not know the spontaneous reporting system and 30% to not know how to report; 54% would rather report an ADR if therapeutic advice was offered. The results indicate that the traditional ways of advertising the srs and communicating with physicians could be improved. Proactive services and professional marketing of srs are needed to reduce underreporting.
In clinical practice, there is a need for a more individualized selection of antidepressants and adequate dosage. The investigation of pharmacokinetically relevant genes is a promising approach to ...assist this selection. In the past 2 years, two commercially available tests have been subject of advertisement, a test from Stada, which analyses variants of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 and a test from HMNC Brain Health, which analyses variants of the ABCB1 gene. The costs for both kits are not covered by the statutory health insurance and it is therefore proposed that the patients are invoiced directly in the form of individual healthcare payment. The companies claim that by applying the tests antidepressant treatment failure can be avoided and that patients will respond faster to the antidepressant used. These claims are not based on appropriate clinical trials, which are either lacking or reveal conflicting results. Hence, the routine use of these tests is not recommended. In accordance with the German S3 Guideline for unipolar depression, therapeutic drug monitoring (TDM) of serum levels should be carried out in cases of non-response to an antidepressant with adequate dosage and duration. As a rule the costs for TDM are covered by the statutory health insurance. Cytochrome P450 genotyping is only indicated when the serum level is not within the expected range and other reasons to explain this discrepancy are excluded. Many laboratories provide these analyses and in individual cases the costs are reimbursed by the statutory health insurance. Further research should be carried out to investigate the importance of the ABCB1 gene for the treatment with antidepressants.
Since the outcome of a meta-analysis depends on which studies are included (Walker et al., 2008), the reasons for the discrepancy between the findings of Nabi et al. and previous meta-analyses may ...depend on the seemingly arbitrary inclusion and exclusion of randomised controlled trials (RCTs) and on an unsatisfactory reinterpretation of data compared to the original publications. ...more RCTs were excluded (N = 15) from the primary analysis than those included (N = 12). ...in a meta-analysis of 31 studies with a total of over 85 000 person-years of risk exposure, Baldessarini et al.
OBJECTIVE: Use of lithium to augment antidepressant medication has been shown to be beneficial in the acute treatment of depression. The authors examined the efficacy of lithium augmentation in the ...continuation treatment of unipolar major depressive disorder. METHOD: Thirty patients with a refractory major depressive episode who had responded to acute lithium augmentation during an open 6-week study participated in a randomized, parallel-group, double-blind, placebo-controlled trial of lithium augmentation during continuation treatment. After a 2-4-week stabilization period following remission, patients were randomly assigned to receive either lithium or placebo for a 4-month period. Antidepressant medication was continued throughout the study. RESULTS: Relapses (including one suicide) occurred in seven (47%) of the 15 patients who received placebo in addition to antidepressants. None (0%) of the 14 patients who received lithium augmentation with antidepressants suffered a relapse during the double-blind phase of the study. Five of the seven relapsing patients in the placebo group developed a depressive episode, and the other two experienced a manic episode. CONCLUSIONS: Lithium augmentation in the continuation phase of treatment of unipolar major depressive disorder effectively protects patients against a relapse. Patients who respond to lithium augmentation should be maintained on lithium augmentation for a minimum of 6 months or even longer.
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