Psychopharmacological treatment with lithium and antiepileptic drugs: suggested guidelines from the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark

Abstract

A subcommittee under the Danish Psychiatric Association and the Child and Adolescent Psychiatric Association in Denmark have recently developed national guidelines for the psychopharmacological treatment with lithium and antiepileptic drugs, and the present translation aims at contributing to the international discussion on the development of proper guidelines for the treatment of bipolar disorder. Among the antiepileptic drugs, the report deals with valproate, carbamazepine and lamotrigine and to a lesser extent with oxcarbazepine, gabapentin and topiramate. The various drugs will be reviewed, outlining the scientific evidence for mood‐stabilizing properties and discussing major side effects, the most important interactions with other drugs and practical use. Special considerations during pregnancy and lactation, during treatment of children and adolescents and during treatment of the elderly will also be presented. Antidepressants and antipsychotics are beyond the scope of the report, but due to the mood‐stabilizing properties of at least some of the atypical antipsychotics, these agents will be brought into some focus in connection with the overall treatment guidelines for the different phases of bipolar disorder given at the end of this report.

Beyond the Guidelines for Bipolar Disorder: Practical Issues in Long-Term Treatment with Lithium

“…32,33 The Danish Psychiatric Association recommends prophylaxis if a patient has had 2 episodes in less than 5 years. 34 All these differ from earlier recommendations of prophylaxis for patients either after 3 episodes, or 2 episodes within 2 years. Using actuarial techniques, Grof et al 35 concluded that at least 2 episodes of mania or depression within 2 years was the best criterion, as this correctly classified 61% of patients as having a future recurrence of illness or not (55% of patients were predicted to have a recurrence within 2 years and they did [true positives] and 6% of patients were predicted not to have a recurrence and they did not [true negatives]).…”

“…If there is recurrence of illness after slowly tapering off of prophylactic medication, then prophylactic treatment should be resumed and continued for many years, or possibly be lifelong. 34 Unfortunately, this appears to be a somewhat arbitrary time frame and does not address individual patient differences, such as number and severity of episodes, suicidality, and degree of impaired functioning. Impaired functioning is frequently related to residual symptoms and may be an indication that treatment needs to be not only continued but also optimized to ensure that the patient achieves complete remission.…”

“…A longer taper may be considered to minimize the risk of relapse. According to the Danish guidelines, 34 acute treatment that has brought mania symptoms under control should be continued for at least a further 3 months.…”

An Updated Review of the Optimal Lithium Dosage Regimen for Renal Protection

“…The World Federation of Societies of Biological Psychiatry suggest that SR preparations may have advantages for tolerability, whereas guidelines from Denmark state that diarrhea may be improved by changing from an SR to an IR preparation. 11,12 These contradictory statements leave the prescriber uncertain about how to dose lithium in a way that optimizes its tolerability profile.…”

“…However, most existing international clinical practice guidelines on the management of BAD provide limited and somewhat contradictory recommendations regarding lithium dosing. 6,7,[10][11][12] For example, the American Psychiatric Association states that SDD regimens may improve peak-related adverse effects, such as tremor, help manage polyuria, and facilitate compliance. 7 However, they also state that lithium is usually started in divided doses to minimize adverse effects.…”