Background: The efficacy of lithium augmentation in therapy-resistant depression has been shown in a series of well-designed, placebo-controlled studies. However, little is known about the predictors ...of a good response to this treatment strategy.
Methods: We retrospectively examined the predictive value of 20 demographic, clinical, biochemical and endocrinological variables using a two-step logistic regression. Seventy-one in-patients with depression refractory to tricyclic antidepressants had received lithium augmentation as part of a standardised treatment protocol.
Results: Within 4 weeks 37 patients (52%) responded to lithium augmentation. Five variables with predictive value were found. Responders were more severely depressed according to the Bech–Rafaelsen Melancholia Scale. The duration of their index episode was shorter. Triiodothyronine serum levels were lower and neuroleptic co-medication and co-diagnosis of personality disorder were less frequent.
Limitations: This was an open, retrospective study.
Conclusions: Severity of depression is a predictor of response to lithium augmentation. This result conflicts with recent studies but is similar to results found in studies of other pharmacological antidepressant strategies.
Objective: This study investigated the impact of latency (the time between illness onset and initiation of prophylactic treatment) on the outcome of prophylaxis in bipolar disorders.
Method: The ...effect of prophylaxis delay (latency) on the course of illness was assessed in 147 patients. Dependent variables were: reduction of days spent in the hospital (prior to vs. during prophylaxis), time to first recurrence, and Morbidity‐Index during prophylaxis (lithium or carbamazepine). Latency and other independent variables were tested using a multivariate approach.
Results: Latency (9.3 years on average) had no significant effect on the subsequent response. Illness severity prior to prophylaxis, however, did predict the relative response. The course of illness during treatment could not be predicted by any one factor.
Conclusion: The delay in initiating prophylaxis appears to have no influence on prophylaxis outcome. Instead, those whose illness was more severe were treated earlier and these patients subsequently showed a relatively greater response. If severity is not controlled for as part of the analysis, latency may be mistaken as an important predictor for response.
In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; ...lithium serum level: 0.63±0.12 mmol/l, carbamazepine dose: 621±186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (
P=0.041) and/or adverse effects (
P=0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years;
P=0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (
P=0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.
Objective: Low platelet monoaminoxidase B (MAO‐B) activity has been associated with various forms of impulsive behaviour and suicidality. The present study investigated the relationship between ...MAO‐B activity in platelets and aspects of suicidality in depressed patients and controls.
Method: In 87 patients with affective spectrum disorders (58% suffering from a major depressive episode – MDE) the potential association between platelet MAO‐B activity and suicidality was examined. Fifty‐nine of the patients had committed suicide attempt recently (SA –‘suicide attempters’), 28 patients were acutely depressed without having shown suicidal thoughts or suicidal behaviour in the past (NA –‘non‐suicide attempters’).
Results: The SA and NA were comparable as to their diagnoses and general demographic and psychopathological parameters. MAO‐B activity did not differ between SA and NA. No systematic correlations existed between MAO‐B activity and any dimensions of suicidal behaviour or psychopathology. As a single finding only a weak positive association of higher MAO‐B activity in SA with a fatal intention of the SA was observed.
Conclusion: Our findings do not support a consistent association of platelet MAO‐B activity and suicidal behaviour in general, but specific facts of suicidality might be associated.
Affective disorders are characterized by first a high recurrence risk, second a 30-50 times increased suicide risk and third a 2- to 3 times increased overall mortality. In contrast to a populistic ...belief no scientific evidence exists that antidepressant treatment, particularly long-term treatment, could reduce the the risk of suicidal acts in depressive patients with a history of suicide attempts. Data, however, coming from international, systematic, retrospective analyses of well-documented long-term courses of illness in reliably diagnosed patients, and from a large national, prospective long-term trial on the prophylactic efficacy of lithium versus carbamazepine and amitriptyline has accumulated in the last 10-15 years strongly supporting a (possibly specific) antisuicidal effect of lithium. The large collaborative IGSLI study (International Group for the Study of Lithium-treated Patients) covering 5,616 patient years clearly showed that adequate long-term lithium treatment significantly reduces and even normalizes the excess mortality of patients with affective disorders. A metaanalysis on 17,000 patients pooled from 28 studies demonstrated that the rate of suicidal acts is 8.6 fold higher in patients without lithium as compared to those with regular lithium treatment. A post-hoc analysis of a large multicenter, controlled long-term trial found no suicidal acts in 146 patients randomized to lithium compared to 9 suicidal acts in 139 patients randomized to carbamazepine. Reanalysis of the data from the IGSLI study supports the concept of the specificity of lithium, i.e., evidence could be provided that lithium also reduces suicidal behavior in patients who do not benefit from the lithium treatment in terms of episode reduction.
Lithium has to be considered as a first line mood stabilizer in affective disorders, particularly in patients with a history of suicide attempts. Extreme caution is required when lithium is discontinued or a patient is switched to another mood stabilizer, because such a patient might have been protected against suicidal impulses in spite of an incomplete response as to the number and quality of depressive/manic episodes.
Suicidal ideations, suicide attempts, and fatal suicides are rare adverse drug reactions to antidepressant drugs, but they essentially are clinically relevant. Drawing on a larger dataset of the ...European drug surveillance program, the present naturalistic study updates a previous contribution (Stübner et al., 2010).
First an analysis of the comprehensive data collected in 81 psychiatric hospitals from 1993 to 2014 by the European drug surveillance program Arzneimittelsicherheit in der Psychiatrie was made. All documented single cases of suicidal ideations or behavior judged as adverse drug reactions to antidepressant drugs were carefully assessed as to their clinical features and drug prescriptions.
Among 219,635 adult hospitalized patients taking antidepressant drugs under surveillance, 83 cases of suicidal adverse drug reactions occurred (0.04%): 44 cases of suicidal ideation, 34 attempted suicides, and 5 committed suicides were documented. Restlessness was present in 42 patients, ego-dystonic intrusive suicidal thoughts or urges in 39 patients, impulsiveness in 22 patients, and psychosis in 7 patients. Almost all adverse drug reactions occurred shortly after beginning antidepressant drug medication or increasing the dosage. Selective serotonin reuptake inhibitors caused a higher incidence of suicidal ideation and suicidal behavior as adverse drug reactions than noradrenergic and specific serotonergic antidepressants or tricyclic antidepressants, as did monotherapy consisting of one antidepressant drug, compared to combination treatments.
The study supports the view that antidepressant drug-triggered suicidal ideation and suicidal behavior (primarily with selective serotonin reuptake inhibitors) are rare. Special clinical features (restlessness, ego-dystonic thoughts or urges, impulsiveness) may be considered as possible warning signs. A combination therapy might be preferable to antidepressant drug monotherapy when beginning treatment.
Bipolar disorder Müller-Oerlinghausen, Bruno; Berghöfer, Anne; Bauer, Michael
The Lancet (British edition),
01/2002, Letnik:
359, Številka:
9302
Journal Article
Recenzirano
Bipolar, or manic-depressive, disorder is a frequent, severe, mostly recurrent mood disorder associated with great morbidity. The lifetime prevalence of bipolar disorder is 1·3 to 1·6%. The mortality ...rate of the disease is two to three times higher than that of the general population. About 10–20% of individuals with bipolar disorder take their own life, and nearly one third of patients admit to at least one suicide attempt. The clinical manifestations of the disease are exceptionally diverse. They range from mild hypomania or mild depression to severe forms of mania or depression accompanied by profound psychosis. Bipolar disorder is equally prevalent across sexes, with the exception of rapid cycling, a severe and difficult to treat variant of the disorder, which arises mostly in women. Because of the high risk of recurrence and suicide, long-term prophylactic pharmacological treatment is indicated. Lithium salts are the first choice long-term preventive treatment for bipolar disorder. They also possess well documented antisuicidal effects. Second choice prophylactic treatments are carbamazepine and valproate, although evidence of their effectiveness is weaker.
In a retrospective 6-year follow-up, we assessed the reasons for and the frequency and consequences of non-adherence in 76 affectively ill patients receiving lithium prophylaxis in two lithium ...clinics. Thirty-eight bipolar (50%), 21 unipolar (27.6%) and 17 schizoaffective patients (22.4%) diagnosed according to DSM-III-R, were investigated with a specialized follow-up documentation. Of the patients 53.9% discontinued prophylaxis at some time; 43.2% of the discontinuations occurred during the first 6 months. In contrast to other studies the main reason reported for non-adherence was resistance against long-term treatment. According to the Lithium Attitudes Questionnaire non-adherent patients showed significantly less acceptance of the prophylaxis in general, of the effectiveness of lithium and of the severity of their illness than adherent patients. In a multivariate analysis of various parameters, only the negative attitude to prophylaxis correlated significantly with non-adherence. Significant correlation was found between treatment outcome and duration of initial prophylaxis. During the 6-year follow-up only the adherent patients showed a significant reduction of the number and duration of admissions. Our findings confirmed non-adherence as a major problem in the effectiveness of lithium prophylaxis. The authors recommend prospective investigations of attitudes and the impact of psychoeducation on long-term adherence.
Beyond its prophylactic efficacy lithium has demonstrated possibly specific antisuicidal effects. Lithium significantly reduces the high excess mortality of patients with affective disorders. ...Appropriate lithium prophylaxis prevents ca. 250 suicides per year in Germany although lithium salts are prescribed within the National Health Scheme at low frequency (0.06% of the population). Rational treatment strategies most likely would demand for about 10 times higher prescription rates. Guidelines and algorithms for selecting an appropriate prophylactic strategy in affective disorders should take into consideration the suicide risk of an individual patient.
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