A decision analysis of long-term lithium treatment and the risk of renal failure.

OBJECTIVE: To establish whether lithium or anticonvulsant should be used for maintenance treatment for bipolar affective disorder (BPAD) if the risks of suicide and relapse were traded off against the risk of end-stage renal disease (ESRD). METHOD: Decision analysis based on a systematic literature review with two main decisions: (1) use of lithium or at treatment initiation and (2) the potential discontinuation of lithium in patients with chronic kidney disease (CKD) after 20 years of lithium treatment. The final endpoint was 30 years of treatment with five outcomes to consider: death from suicide, alive with stable or unstable BPAD, alive with or without ESRD. RESULTS: At the start of treatment, the model identified lithium as the treatment of choice. The risks of developing CKD or ESRD were not relevant at the starting point. Twenty years into treatment, lithium still remained treatment of choice. If CKD had occurred at this point, stopping lithium would only be an option if the likelihood of progression to ESRD exceeded 41.3% or if anticonvulsants always outperformed lithium regarding relapse prevention. CONCLUSION: At the current state of knowledge, lithium initiation and continuation even in the presence of long-term adverse renal effects should be recommended in most cases.

The assessment and treatment of water imbalance in patients with psychosis.

Polydipsia and episodic life-threatening water intoxication remain important clinical problems for a significant portion of persons with schizophrenia. The disorders are associated with increased morbidity and mortality from a number of causes. With a basic understanding of the pathophysiology, one can easily diagnose and assess the clinical conditions. We review here the scope and pathophysiology of disordered water imbalance, including both primary and secondary polydipsia and hyponatremia. Reversible factors and possible interventions are reviewed. Treatment options for preventing water intoxication have expanded from discontinuation of offending agents, targeted fluid restriction, and clozapine therapy to the addition of oral vasopressin antagonists. The latter, however, are extremely potent and must be carefully monitored.

Depressive illness burden associated with complex polypharmacy in patients with bipolar disorder: findings from the STEP-BD.

BACKGROUND: Many patients with bipolar disorder receive multi-drug treatment regimens, but the distinguishing profiles of patients who receive complex pharmacologies have not been established. METHOD: Prescribing patterns of lithium, anticonvulsants, antidepressants, and antipsychotics were examined for 4,035 subjects with bipolar disorder (DSM-IV) immediately prior to entering the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Subjects were recruited for participation across 22 centers in the United States between November 1999 and July 2005. The quality receiver operating characteristic (ROC) method was used to develop composite profiles of patients receiving complex regimens (p < .01 for all iterations). RESULTS: Use of 3 or more medications occurred in 40% of subjects, while 18% received 4 or more agents. Quality ROC analyses revealed that subjects had a 64% risk for receiving a complex regimen (> or = 4 medications) if they had (1) ever taken an atypical antipsychotic, (2) > or = 6 lifetime depressive episodes, (3) attempted suicide, and (4) an annual income > or = $75,000. Complex polypharmacy was least often associated with lithium, divalproex, or carbamazepine and most often associated with atypical antipsychotics or antidepressants. Contrary to expectations, a history of psychosis, age at onset, bipolar I versus II subtype, history of rapid cycling, prior hospitalizations, current illness state, and history of alcohol or substance use disorders did not significantly alter the risk profiles for receiving complex regimens. CONCLUSION: Complex polypharmacy involving at least 4 medications occurs in approximately 1 in 5 individuals with bipolar disorder. Use of traditional mood stabilizers is associated with fewer cotherapies. Complex regimens are especially common in patients with substantial depressive illness burden and suicidality, for whom simpler drug regimens may fail to produce acceptable levels of response. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00012558.

Discovery and development of lamotrigine for bipolar disorder: a story of serendipity, clinical observations, risk taking, and persistence.

This paper briefly reviews and comments on the development of lamotrigine as a treatment for bipolar disorder. The events described include astute clinical observations by epileptologists, serendipitous coupling of the drug's clinical profile to unmet need of two refractory bipolar patients by a practicing psychiatrist, risk taking on the part of an industry sponsor, and persistence on the part of a few key internal and external advocates to see development through to its conclusion, taking place against a backdrop of a disease area which, at the time of the earliest events described here, had not seen the development of any new pharmacologic treatments for decades. Fortunately for patients, since that time there has been a veritable explosion of research into treatments for bipolar disorder, both old and new, so that now patients and physicians have multiple evidence-based options for the treatment of this devastating illness. The development of lamotrigine provides one example of the importance of prescience, patience and persistence in bringing a novel idea to clinical fruition.

Pharmacological treatment of acute mania in psychiatric in-patients between 1994 and 2004.

BACKGROUND: In a cross-section approach we investigated prescription practice in acute mania in 63 German, Swiss and Austrian hospitals between 1994 and 2004. METHODS: Our data were gathered from a large drug safety program (AMSP) within which on two reference days each year all administered drugs are recorded. For the present study, all cases with a primary diagnosis of acute euphoric mania (n=1291) or mixed-state mania (n=143) were identified. Prescription rates from two periods, 1994 to 1999 and 2000 to 2004, were compared. RESULTS: In euphoric mania, prescription of lithium decreased by about one-fifth (43.3% to 34.5%, p<0.01), while prescription of anticonvulsants increased by one-half (from 40.0% to 60.7%, p<0.001). Administration of atypical antipsychotics more than doubled (18.5% to 43.9%, p<0.001), while use of typical antipsychotics decreased significantly (56.9% to 27.8%, p<0.001). Overall prescription rates of antipsychotics (79.6% vs. 81.6%) and antidepressants (14.0% vs. 15.5%) remained stable, while administration of tranquilizers increased significantly (26.3% to 34.3%, p<0.01). In mixed-state mania, similar trends over time to those seen in euphoric mania were observed for lithium (43.2% to 33.3%), anticonvulsants (50.0% to 69.7%, p<0.05) and tranquilizers (22.7% to 40.4%). Prescription rates of antipsychotics slightly increased (63.6% to 72.7%), while prescription of antidepressants slightly decreased (54.5% to 46.5%). Polypharmacy was a common phenomenon: patients with euphoric mania were treated with a mean number of 2.9+/-1.2 psychotropic agents, and patients with mixed-state mania with 3.3+/-1.5 psychotropic agents. Both groups showed a significant increase over time. Second-generation atypical antipsychotics were adopted quite rapidly for the treatment of acute mania considering the availability of the scientific evidence at that time. Off-label use was a common phenomenon. Deviations from recommended guidelines were found mainly in the use of antidepressant and antipsychotic drugs both in mixed-state and euphoric mania. CONCLUSIONS: Naturalistic prescription studies like this may encourage a critical scrutiny of clinical treatment habits and may also drive further research thus moderating potential differences between evidence-based knowledge and everyday clinical practice.

Subclinical hypothyroidism in lithium-treated psychiatric patients in Tehran, Islamic Republic of Iran.

We investigated thyroid function in 46 (20 female & 26 male) psychiatric outpatients on lithium treatment by assessing triiodothyronine, thyroxine and thyroid stimulating hormone (TSH) levels. The presence of thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) was also assessed. Out of the 46 patients, 8 (17%) displayed overt hypothyroidism. Of the remaining patients, subclinical hypothyroidism was found in 16 patients (35%) and euthyroidism in 22 (48%). Thyroid antibodies were present in 6 patients in the euthyroid group and 5 patients in the hypothyroid group. The Pearsor product-moment correlation results indicated positive association between TSH level and duration of lithium use and age of the patients with subclinical hypothyroidism. Duration of lithium use and age could be a reasonable indicator for screening asymptomatic patients for subclinical hypothyroidism after starting lithium treatment.

Long-term therapy with lithium in a private practice clinic: a naturalistic study.

OBJECTIVE: To document the effectiveness and vicissitudes of treating 14 bipolar patients with lithium carbonate over a combined 300 years, and an average of 21 years/patient. METHODS: Chart review of the narrative and laboratory studies of these 14 patients ranging in duration from 12 to 29 years. RESULTS: Lithium stabilized these bipolar patients over these periods. Only three patients required hospitalization, one because lithium was slowly tapered at her request after 6 years of mood stability, another because of non-compliance, and a third because of co-morbid alcohol abuse. One patient attempted suicide after lithium was tapered off. However, in some patients, there were serious side-effects necessitating lithium discontinuation. CONCLUSIONS: Controlled studies in psychopharmacology are obviously preferred to open-label or naturalistic case studies. However, controlled studies are rarely conducted over long periods, and practice-related naturalistic research can be of value, albeit anecdotal and without the use of structured rating scales. In this paper, we are reporting on 14 patients seen consistently by one psychiatrist. These patients were functional and productive at work and in family life. The patients suffered brief hypomanic or depressive episodes. Although several patients experienced serious side-effects, lithium was continued with stable mood, while the side-effects were managed in collaboration with other specialists.

Incident monitoring in psychiatry.

Critical Incident Monitoring (CIM) as an instrument of quality assurance (QA) has received increasing attention in recent years. The present study was developed to explore a potential role for CIM in QA for clinical psychiatry. A questionnaire was sent to psychiatrists and requested retrospective reporting of clinical incidents, and a pilot study of an inpatient-based incident reporting system was performed. All Fellows of the Royal Australian and New Zealand College of Psychiatry (RANZCP) were sent a questionnaire. Eight psychiatric inpatient services were invited to participate in the pilot study. The returns of the questionnaires were aggregated and analysed to reveal a relatively small number of separate incident types, with little difference between the 'adverse outcome' and 'near-miss' categories. Similar results were found with the pilot study. It was concluded that the development of a unified incident reporting system for use by psychiatric clinicians and psychiatric services may add usefully to existing quality improvement processes.

Decision model for the acute treatment of mania.

Decision making in psychiatric diagnosis and treatment has not been evaluated systematically. The authors present a model for treatment of an acute manic episode using a decision analysis software program. Six treatment options were put into the model: lithium, valproate, carbamezepine, electroconvulsive therapy, clonazepam, and neuroleptics. Each treatment was evaluated on three factors, efficacy, tolerability, and cost, using data from the literature and pharmacy and billing information. Output from the computer program identified three top choices among the six options: valproate, carbamazepine, and lithium, with valproate emerging as the first choice using the data we inputted.