[Show abstract][Hide abstract] ABSTRACT: Lithium and with restrictions, carbamazepine, valproic acid, lamotrigine, olanzapine, aripiprazole and quetiapine, are approved in Germany for maintenance treatment of bipolar disorder. Lithium is the only drug that (I) proved to be effective for the prevention of depressive as well as manic episodes in state-of-the-art studies without an enriched design and that (II) is approved for the maintenance treatment of bipolar disorders without restrictions. It (III) is also the only drug which is recommended for maintenance treatment by the current German S3 guidelines on bipolar disorders with the highest degree of recommendation (A) and (IV) is the only drug with a well proven suicide preventive effect. Hence, lithium is the mood stabilizer of first choice. No patient should be deprived of lithium without a specific reason. Side effects and risks are manageable if both the physician and the patient are well informed. Detailed and practical information on a safe use of lithium can be found in the S3 guidelines on bipolar disorders. For patients who do not respond sufficiently to lithium, have contraindications or non-tolerable side effects, other mood stabilizers should be used. Restrictions in their respective approval as well as specific side effects and risks have to be taken into account. Because maintenance treatment is a long-term treatment, particular concern should be paid to drugs with the potential risk of a metabolic syndrome, particularly atypical antipsychotics.
[Show abstract][Hide abstract] ABSTRACT: Recent high-quality studies have confirmed the central role of lithium in the treatment of bipolar disorder and have established lithium as the drug of first choice for long-term prophylaxis in this condition. However, several indications for its use in unipolar major depression are also based on sound evidence. This includes lithium augmentation as a main strategy for depressed patients not responding to an antidepressant, lithium prophylaxis for recurrent unipolar depression as an alternative to prophylaxis with an antidepressant, and lithium's unique anti-suicidal properties. Lithium monotherapy, on the other hand, is not established for acute treatment of depression. Lithium therapy should be a core competency of every psychiatrist, enabling the safe use of lithium, to the benefit of our patients.
[Show abstract][Hide abstract] ABSTRACT: Bipolar depression and its clinical presentation is a frequent but complex psychiatric disease. Despite the high prevalence and the clinical and economic relevance of bipolar depression, few treatments are proven to be highly and consistently effective. In practice, the treatment of bipolar depression typically includes complex treatment decision-making. The best evidence for a pharmacological treatment exists for quetiapine. Alternatives with limitations are lamotrigine (also in the combination with lithium), carbamazepine and olanzapine. The effectiveness and recommendation of antidepressants in the treatment of bipolar depression remains controversial. Initially, depressive episodes should been treated with one of the named substances with antidepressant properties. In non-responders, a combination of lithium and lamotrigine, or antidepressants in combination with either lithium, an antiepileptic drug or atypical antipsychotics, may be necessary. If a depressive episode occurs under ongoing mood-stabilizing treatment, combination treatments of different substances, even with antidepressants, can be necessary. In the case of treatment-resistant depressive episodes, complex treatment strategies (combination therapies, MAO inhibitors) should be considered. This review describes the treatment recommendations of different guidelines for bipolar depression and emphasizes their differences. Furthermore, alternative pharmacological treatment strategies and complex treatment situations are discussed.
[Show abstract][Hide abstract] ABSTRACT: Treatment of bipolar depression requires complex treatment decisions in daily routine care. The best evidence for pharmacological treatment is given for quetiapine and with limitations also in off-label use for lamotrigine, especially in combination with lithium, carbamazepine and olanzapine. Effectiveness and recommendation of antidepressants in treatment of bipolar depression remain controversial because of insufficient data. Initially, in depressive episodes a phase prophylactic treatment should be initiated or (if already existing) optimized and more severe episodes should be treated with the substances described before. In case of non-response, the combination of lithium and lamotrigine or antidepressants in combination with lithium, antiepileptics or atypical antipsychotics may be necessary. If depressive episodes occur in the course of pharmacological treatment with prophylactic agents, combination therapies of different substances, even with antidepressants, are necessary. In case of treatment-resistant depressive episodes, complex treatment strategies (e.g. combination therapies and MAO inhibitors) should be considered.
[Show abstract][Hide abstract] ABSTRACT: In recent years, lithium has proved an effective augmentation strategy of antidepressants in both acute and treatment-resistant depression. Neuroprotective and procognitive effects of lithium have been evidenced. Brain-derived neurotrophic factor (BDNF) has been shown to play a key role in the pathophysiology of several neurological and psychiatric disorders. The BDNF hypothesis of depression postulates that a loss of BDNF is directly involved in the pathophysiology of depression, and its restoration may underlie the therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic factor serum concentrations were measured in a total of 83 acutely depressed patients before and after 4 weeks of lithium augmentation. A significant BDNF increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived neurotrophic factor concentrations at baseline correlated negatively with relative Hamilton Depression Scale change after treatment with lithium (n = 83; r = -0.23; P < 0.05). This is the first study showing that lithium augmentation of an antidepressant strategy can increase BDNF serum concentrations. Our study replicates previous findings showing that serum BDNF levels in patients with depressive episodes increase during effective antidepressant treatment. Further studies are needed to separate specific effects of different antidepressants on BDNF concentration and address potential BDNF downstream mechanisms.
Journal of clinical psychopharmacology 09/2013; · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lithium is the only drug that obtained the highest level of recommendation for maintenance therapy in the recent German S3 guidelines on bipolar disorders. In addition it is the only drug with proven efficacy for the prevention of manic as well as depressive episodes in studies with a non-enriched design. Therefore, it is highly welcomed that The Lancet recently published a systematic review and meta-analysis on the risks and side effects of lithium. This is the most comprehensive review on this topic so far.The glomerular filtration rate and maximum urinary concentration ability are slightly reduced under lithium. More patients suffered from renal failure compared to controls; however, renal failure remains a very rare event. The review confirmed the well known suppressive effects of lithium on the thyroid. An increase of serum calcium could be observed relatively frequently, therefore, regular control of serum calcium under lithium therapy is recommended. A relevant increase in body weight is more frequent under lithium than under placebo but less frequent than under olanzapine. No statistically significant increase could be found for hair loss, skin disorders or major congenital abnormalities.Lithium treatment is a safe therapy when clinicians follow the established recommendations. Data indicate that a risk for renal failure exists especially in patients without regular monitoring or with too high lithium serum levels. A (subclinical) hypothyroidism is not an indication to stop administration of lithium but is an indication for l-thyroxin substitution therapy. In pregnancy the risks of continuing lithium should be balanced against the risks of stopping lithium together with the patient.
[Show abstract][Hide abstract] ABSTRACT: Objective: In many countries diphenhydramine (DPH) is commonly available over the counter, frequently used, and generally regarded as a harmless drug. It is used as a sedative, antiallergic or antiemetic substance.Methods: We present a systematic review of literature search in Pubmed from 1972 to 2012 describing DPH addiction. The literature search in reveals that the addictive potential of DPH can be regarded as proved, based on cases series, eight case reports, a pharmacological overview, one uncontrolled, and one randomized, placebo controlled study. In addition we report a case of an abstinent alcoholic patient treated in our department for DPH-dependency.Conclusion: Especially when treating patients with a history of addiction, physicians should consider and check the possibility of a DPH dependency.
[Show abstract][Hide abstract] ABSTRACT: Bipolar disorder is a serious mental illness, characterized by frequent recurrences and major comorbidities. Its consequences can include suicide.
An S3 guideline for the treatment of bipolar disorder was developed on the basis of a systematic literature search, evaluation of the retrieved publications, and a formal consensus-finding procedure. Several thousand publications were screened, and 611 were included in the analysis, including 145 randomized controlled trials (RCT).
Bipolar disorder should be diagnosed as early as possible. The most extensive evidence is available for pharmacological monotherapy; there is little evidence for combination therapy, which is nonetheless commonly given. The appropriate treatment may include long-term maintenance treatment, if indicated. The treatment of mania should begin with one of the recommended mood stabilizers or antipsychotic drugs; the number needed to treat (NNT) is 3 to 13 for three weeks of treatment with lithium or atypical antipsychotic drugs. The treatment of bipolar depression should begin with quetiapine (NNT = 5 to 7 for eight weeks of treatment), unless the patient is already under mood-stabilizing treatment that can be optimized. Further options in the treatment of bipolar depression are the recommended mood stabilizers, atypical antipsychotic drugs, and antidepressants. For maintenance treatment, lithium should be used preferentially (NNT = 14 for 12 months of treatment and 3 for 24 months of treatment), although other mood stabilizers or atypical antipsychotic drugs can be given as well. Psychotherapy (in addition to any pharmacological treatment) is recommended with the main goals of long-term stabilization, prevention of new episodes, and management of suicidality. In view of the current mental health care situation in Germany and the findings of studies from other countries, it is clear that there is a need for prompt access to need-based, complex and multimodal care structures. Patients and their families need to be adequately informed and should participate in psychiatric decision-making.
Better patient care is needed to improve the course of the disease, resulting in better psychosocial function. There is a need for further high-quality clinical trials on topics relevant to routine clinical practice.
Deutsches Ärzteblatt International 02/2013; 110(6):92-100. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is increasing evidence from ecological studies that lithium levels in drinking water are inversely associated with suicide mortality. Previous studies of this association were criticized for using inadequate statistical methods and neglecting socioeconomic confounders. This study evaluated the association between lithium levels in the public water supply and county-based suicide rates in Texas. A state-wide sample of 3123 lithium measurements in the public water supply was examined relative to suicide rates in 226 Texas counties. Linear and Poisson regression models were adjusted for socioeconomic factors in estimating the association. Lithium levels in the public water supply were negatively associated with suicide rates in most statistical analyses. The findings provide confirmatory evidence that higher lithium levels in the public drinking water are associated with lower suicide rates. This association needs clarification through examination of possible neurobiological effects of low natural lithium doses.
Journal of Psychiatric Research 01/2013; · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lithium ist die einzige Substanz, die in der aktuellen S3-Leitlinie zur Diagnostik und Therapie Bipolarer Störungen den höchsten Empfehlungsgrad zur Phasenprophylaxe bipolarer Störungen erhält und die in Studien ohne sog. ,,enriched design“ die Wirksamkeit zur Prävention sowohl manischer als auch depressiver Episoden zeigen konnte. Es ist daher begrüßenswert, dass in The Lancet nun mit einer systematischen Übersichtsarbeit und Metaanalyse die bislang umfangreichste Auswertung der Erkenntnisse zu unerwünschten Wirkungen und Risiken einer Lithiumbehandlung publiziert wurde.Es zeigten sich eher geringe Einschränkungen der glomerulären Filtrationsrate und der maximalen Urinkonzentrationsfähigkeit sowie eine erhöhte Rate an terminaler Niereninsuffizienz bei mit Lithium behandelten Patienten im Vergleich zu Kontrollen. Letzteres allerdings auf sehr niedrigem Niveau. Die bekannten thyreostatischen Lithiumeffekte wurden bestätigt. Relativ häufig kommt es zum Ansteigen des Kalziumspiegels, weshalb auch dieser regelmäßig während einer Lithiumtherapie kontrolliert werden sollte. Eine relevante Gewichtszunahme tritt signifikant häufiger auf als unter Placebo, aber seltener als unter Olanzapin. Kein statistisch signifikant häufigeres Auftreten unter Lithium konnte für Haarausfall, Hautveränderungen und kongenitale Fehlbildungen gefunden werden.Unter Beachtung der etablierten Anwendungsempfehlungen stellt eine Lithiumbehandlung eine sichere Therapie dar. Es gibt Hinweise darauf, dass die gefürchtete terminale Niereninsuffizienz vor allem bei mangelhaft kontrollierter oder mit zu hohen Serumspiegeln durchgeführter Behandlung auftritt. Eine (latente) Hypothyreose ist kein Grund zum Absetzen von Lithium, sondern eine Indikation für eine L-Thyroxin-Behandlung. Im Falle einer Schwangerschaft unter Lithium sollten Risiken der Fortführung von Lithium mit denen des Absetzens gemeinsam mit der Schwangeren abgewogen werden.
Der Nervenarzt 01/2013; 84(7). · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies of the 1970s and 1980s showed lithium monotherapy to be an effective treatment of acute unipolar major depressive disorder (MDD) and hence as a potential alternative to monoaminergic antidepressants.The objective was to conduct the first comparison of a lithium monotherapy with a modern antidepressant in the acute treatment of MDD. Results were compared with citalopram's efficacy as shown in a different but methodologically identical study (including same researchers, same time, and same place).Thirty patients with an acute MDD (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM IV] I) were treated with lithium monotherapy (study 1) or with citalopram monotherapy (study 2, N = 32) for 4 weeks.Response rates (decrease in Hamilton Depression Rating Scale score >50%) were 50% for lithium and 72% for citalopram (P = 0.12). Citalopram-treated subjects showed a greater decrease in Hamilton Depression Rating Scale scores (significant at 2 weeks). In the lithium study, only patients with a recurrent episode (DSM-IV: 296.3) responded (15/22), as opposed to none of 8 patients with a first/single episode (DSM-IV: 296.2) (P = 0.002). Patients with a single episode responded significantly more often to citalopram than to lithium (P = 0.007). Both drugs were well tolerated. Only one patient (citalopram) terminated the study prematurely owing to adverse effects.Our results do not support the use of lithium as an alternative to SSRI in the treatment of acute MDD. The finding of a better response to lithium in patients with a recurrent depression has not been reported before and warrants replication. The comparison is limited by the lack of a randomized double-blind design.
Journal of clinical psychopharmacology 12/2012; · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antipsychotics, when used to treat neuropsychological symptoms associated with dementia, are associated with low effectiveness but a high risk of side effects. Some of these unwanted effects are severe and include an increased rate of cerebrovascular events and increased mortality. Although neuropsychiatric symptoms are frequently associated with dementia, it appears that antipsychotics are often used without clear indications and for too long time periods. Antipsychotics should be used only when all non-pharmacological strategies have failed. A clear definition of the treatment target in advance and a continuous monitoring of the therapy are mandatory.
[Show abstract][Hide abstract] ABSTRACT: Non-response to an antidepressant monotherapy in unipolar depression is quite common. Therefore strategies for subsequent treatment steps are necessary. However, there is a lack of direct comparisons of these different strategies. In this naturalistic study we compared the outcome to different strategies after failure of the primary antidepressant treatment.Failure of primary antidepressant monotherapy occurred in 135 patients. 98 of these patients have been administered 4 treatment strategies of the physicians' choice: lithium augmentation (Li-Augm), switching to another antidepressant (AD-Switch), combination of 2 antidepressants (AD-Comb) or augmentation with second generation antipsychotic (SGA-Augm). Primary outcome measure was the 17-item Hamilton rating scale for depression (HRSD).Patients who received Li-Augm or augmentation with SGAs showed significantly greater improvement in HRSD and BDI compared to patients with antidepressant switch or antidepressant combination. Remission rates for Li-Augm and SGA-Augm were 89.3% and 86.2% compared to 40.7% for AD-Switch and 42.9% for AD-Comb.Changing to another pharmacological class (Li-Augm or augmentation with SGAs) showed better treatment results than sticking to the class of antidepressants (AD-Switch and AD-Comb) after primary failure in response to antidepressant monotherapy in unipolar depression. The lack of randomization and absence of a non-response definition are design flaws. Controlled studies are required to confirm the findings of this trial.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Recent reports indicate that the prevalence of bipolar disorder (BD) in patients with an acute major depressive episode might be higher than previously thought. We aimed to study systematically all patients who sought therapy for major depressive episode (MDE) within the BRIDGE study in Germany, reporting on an increased number (increased from 2 in the international BRIDGE report to 5) of different diagnostic algorithms. METHODS: A total of 252 patients with acute MDE (DSM-IV confirmed) were examined for the existence of BD (a) according to DSM-IV criteria, (b) according to modified DSM-IV criteria (without the exclusion criterion of 'mania not induced by substances/antidepressants'), (c) according to a Bipolarity Specifier Algorithm which expands the DSM-IV criteria, (d) according to HCL-32R (Hypomania-Checklist-32R), and (e) according to a criteria-free physician's diagnosis. RESULTS: The five different diagnostic approaches yielded immensely variable prevalences for BD: (a) 11.6; (b) 24.8%; (c) 40.6%; (d) 58.7; e) 18.4% with only partial overlap between diagnoses according to the physician's diagnosis or HCL-32R with diagnoses according to the three DSM-based algorithms. CONCLUSIONS: The diagnosis of BD in patients with MDE depends strongly on the method and criteria employed. The considerable difference between criteria-free physician's diagnosis and the remaining algorithms indicate the usefulness of criteria lists within the everyday clinical setting. LIMITATIONS: Diagnoses based on DSM were only made with checklists. The diagnoses of (hypo-) manic episodes in the patient history were not systematically verifiable by indirect anamnesis.
Journal of affective disorders 09/2012; · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antiepileptics have been shown to reduce alcohol intake or to prevent relapse in patients with alcoholism.
To investigate if the new antiepileptic levetiracetam (LEV) prevents relapse after detoxification compared with placebo in patients with alcohol dependence.
Two hundred one patients were included in the prospective, randomized, double-blind, multicenter, placebo-controlled trial. After detoxification treatment and a screening period of 7 days, patients were randomized to treatment with LEV or placebo. Medication was administered in a fixed-dose schedule for 16 weeks. Primary outcome parameters were the overall rate and time to relapse with heavy drinking. Secondary outcome parameters were time to the first drink, craving, adherence, tolerability, and safety data (mean corpuscular volume, serum alanine aminotransferase, serum aspartate aminotransferase, γ-glutamyltransferase).
The rate of relapse and the time to relapse did not differ significantly between both groups, but less patients treated with LEV terminated treatment early compared with patients receiving placebo. Tolerability and safety data were similar in the LEV group compared with placebo.
Our data do not support a significant effect of LEV on relapse prevention in patients with alcohol dependence during the first 16 weeks of abstinence.
Journal of clinical psychopharmacology 06/2012; 32(4):558-62. · 5.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bipolar disorders are severe psychiatric disorders with extensive individual and health economic consequences. Starting in 2007 the first German evidence and consensus based guideline for diagnostics and treatment of bipolar disorders was developed which holds the potential of increasing confidence of therapists, patients and relatives in the decision-making process and improving healthcare service experiences of patients and relatives. Apart from recommendations for diagnostics and treatment the guidelines provide those for trialogue action, knowledge transfer and self-help and for strategies for healthcare provision of this complex disorder. In the present article the methodology and essential recommendations are outlined and complemented in specific topics by corresponding articles in this special issue. Due to restrictions of the length of this presentation there is the need to refer to the comprehensive version of the guidelines at several points also regarding a detailed discussion of the limitations.
Der Nervenarzt 05/2012; 83(5):568-86. · 0.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: Alcoholism ultimately leads to impairment of memory and other cognitive functions. This can interfere with treatment, if cognitively impaired alcohol-dependent individuals have difficulties recalling and implementing skills acquired during therapy. We investigate if alcohol-dependent individuals without clinically apparent withdrawal symptoms may still be impaired in higher-order cognitive functions. Methods: Thirty-four alcohol-dependent patients and 20 matched healthy controls were tested with the Verbal Learning and Memory Test which includes seven measurement points. The test comprises free recall, free recall after distraction and after 30 minute delay, and a word recognition task. Testing was performed between day seven and day 10 after the beginning of abstinence, when clinical withdrawal symptoms had ceased. Results: Compared to healthy controls, alcohol-dependent patients performed worse in free recall after delay, but not in word recognition. Healthy controls showed a more linear progression of improvement in verbal memory performance. Overall, alcohol-dependent individuals showed reduced verbal learning efficiency. The extent of impaired recall after distraction was positively associated (one-tailed test) with history of delirium (r = 0.34, p = 0.04), seizures (r = 0.46, p = 0.01), and years since diagnosis for alcohol dependency (r = 0.39, p = 0.01). Conclusions: Our results provide evidence that unmedicated alcohol-dependent patients without obvious withdrawal symptoms had impaired verbal recall, but normal recognition performance, at seven to 10 days after onset of abstinence. This deficit may deteriorate treatment outcomes due to poorer implementation of skills newly-learned during this time period. (PsycINFO Database Record (c) 2013 APA, all rights reserved) (journal abstract)
Irish journal of psychological medicine 01/2012; 29(2):96-101.