Divalproex utility in bipolar disorder with co-occurring cocaine dependence: a pilot study

OBJECTIVE: The aim of this open-label pilot study was to evaluate the utility of divalproex in decreasing cocaine use and stabilizing mood symptoms among patients with bipolar disorder with comorbid cocaine dependence. METHOD: Fifteen patients enrolled in the study and seven met final inclusion criteria of DSM-IV/SCID diagnoses of bipolar I disorder and comorbid cocaine dependence with active cocaine use. Patients were started on open-label divalproex. After stabilization on divalproex sodium, weekly assessments were undertaken for 8weeks. Subjects also attended dual recovery counseling. RESULTS: The results revealed significant improvement on % cocaine abstinent days, dollars spent on cocaine, ASI's drug use severity index, % alcohol abstinent days, drinks per drinking day, marijuana use and cigarettes smoking. They also had significant improvement on manic, depressive, and sleep symptoms and on functioning. There were no reported adverse events or increases in liver function tests. CONCLUSION: The results of this open-label study point to the potential utility of divalproex in patients with bipolar disorder and primary cocaine dependence. Double-blind, placebo-controlled studies to fully evaluate the efficacy of divalproex in this high risk clinical population are warranted.     

Lamotrigine in the treatment of bipolar disorder

Lamotrigine is a novel anticonvulsant agent that has recently been introduced as a long-term treatment in bipolar disorder. Its role in the treatment of epilepsy is based on its actions to decrease ion channel conductance and antagonise glutamatergic function. Therefore, it has a mode of action unlike other agents used on a long-term basis in mood disorders. The evidence for efficacy is stronger for the prevention of depressive, rather than manic, episodes. The pivotal trials are in bipolar I disorder, but there is interest in its actions in patients with bipolar II and spectrum conditions. Its efficacy in other psychiatric conditions remains to be properly established. It is well tolerated and, with careful prescribing, the incidence of rash occurs no more than with placebo; however this is still a concern. Although usually well tolerated, headache, insomnia and drowsiness are probably the most common side effects.     

Lamotrigine in the treatment of bipolar disorder

Lamotrigine has undergone a remarkable series of systematic studies since 1994 that now establish it as an efficacious, well-tolerated treatment in bipolar disorder. Its efficacy principally addresses both acute and maintenance phase benefits on depressive symptomatology. These benefits have been demonstrated in placebo-controlled studies, rapid cycling patients, bipolar I and II patients and monotherapy as well as in combination therapy, although this has been less well studied. The drug is exceptionally well-tolerated in long-term treatment, although initial dosing requires gradual dosage escalation to avoid the risk of inducing serious rashes with features within the spectrum of Stevens–Johnson syndrome. Administration with valproate requires a slower dosage titration, whereas, as with many drugs, administration with carbamazepine requires a more rapid dosage increase. In contrast to marketed antidepressants, lamotrigine appears not to induce manic or hypo-manic episodes, nor to increase cycling frequency. This combination of properties makes it a first-choice treatment for acute bipolar depression and continuation treatment, especially, but not limited to, prophylaxis against recurrent depression and depressive symptoms. Lamotrigine appears not to have acute antimanic properties. A small number of studies suggest a broader spectrum of efficacy, including in some axis I disorders that are comorbidly associated with bipolar disorder.     

Lamotrigine in the treatment of bipolar disorder

Lamotrigine is a novel anticonvulsant agent that has recently been introduced as a long-term treatment in bipolar disorder. Its role in the treatment of epilepsy is based on its actions to decrease ion channel conductance and antagonise glutamatergic function. Therefore, it has a mode of action unlike other agents used on a long-term basis in mood disorders. The evidence for efficacy is stronger for the prevention of depressive, rather than manic, episodes. The pivotal trials are in bipolar I disorder, but there is interest in its actions in patients with bipolar II and spectrum conditions. Its efficacy in other psychiatric conditions remains to be properly established. It is well tolerated and, with careful prescribing, the incidence of rash occurs no more than with placebo; however this is still a concern. Although usually well tolerated, headache, insomnia and drowsiness are probably the most common side effects.     

Lamotrigine in the treatment of bipolar disorder

Lamotrigine has undergone a remarkable series of systematic studies since 1994 that now establish it as an efficacious, well-tolerated treatment in bipolar disorder. Its efficacy principally addresses both acute and maintenance phase benefits on depressive symptomatology. These benefits have been demonstrated in placebo-controlled studies, rapid cycling patients, bipolar I and II patients and monotherapy as well as in combination therapy, although this has been less well studied. The drug is exceptionally well-tolerated in long-term treatment, although initial dosing requires gradual dosage escalation to avoid the risk of inducing serious rashes with features within the spectrum of Stevens-Johnson syndrome. Administration with valproate requires a slower dosage titration, whereas, as with many drugs, administration with carbamazepine requires a more rapid dosage increase. In contrast to marketed antidepressants, lamotrigine appears not to induce manic or hypo-manic episodes, nor to increase cycling frequency. This combination of properties makes it a first-choice treatment for acute bipolar depression and continuation treatment, especially, but not limited to, prophylaxis against recurrent depression and depressive symptoms. Lamotrigine appears not to have acute antimanic properties. A small number of studies suggest a broader spectrum of efficacy, including in some axis I disorders that are comorbidly associated with bipolar disorder.     

Divalproex in the treatment of migraine

Valproic acid has been used in the treatment of migraine headache for nearly 20 years. During this period of use several additional delivery modes have been developed to either improve tolerability or patient compliance with the divalproex sodium formulation and the extended-release formulation of divalproex sodium. Additionally, an intravenous formulation has become available which permits rapid achievement of therapeutic levels of the drug. There have been a number of reports on the use of valproic acid in migraine and other headache disorders, suggesting it to be an efficacious treatment. This paper reviews the results of the published reports of valproic acid in migraine and other headache disorders, including open-label studies, comparator trials, and double-blind, placebo-controlled trials. These studies have been conducted with the various formulations of valproic acid that have been on the market. The papers utilized in this study were obtained though Medline searches on valproic acid and divalproex sodium coupled with the various headache disorders. Additionally, the CD-ROM of past issues of Headache and Cephalalgia was reviewed for similar keywords. Lastly, the indices of the journal Headache Quarterly were reviewed for additional articles on valproic acid and divalproex sodium. Valproic acid in its various formulations has been demonstrated to be an efficacious and well-tolerated agent for the preventive treatment of migraine, chronic daily headache, and cluster headache. Additionally, it has been demonstrated to be efficacious and well tolerated in treating acute migraine attacks when given as an intravenous solution.     

Antipsychotic medications in the treatment of bipolar disorder

Antipsychotic medications have been used to treat acute phases, and prevent relapses in, bipolar illness since their introduction into psychiatric practice. With the introduction of second generation antipsychotic medications, there has been renewed interest in the utility of this class of medications in managing manic-depression. It appears that all antipsychotic agents investigated have a potent acute antimanic property. This has been shown both in monotherapy and in combination with traditional mood stabilizing medications. The first generation antipsychotics appeared to worsen depression or induce a depressive-like state, but the second generation agents do not have this property and may have some antidepressant properties in bipolar patients. There is a dearth of controlled long term studies, but in open studies, both first and second generation agents appear to have a beneficial effect. Second generation antipsychotic agents appear to be a useful tool that may benefit bipolar patients. Adverse consequences of this group of medications appear to be the major limiting factors to their use. Antipsychotic medications play a very important role in the treatment of bipolar illness. This has become especially true since the introduction of second generation agents. There is a wealth of data documenting the use of these agents in bipolar mania. There are fewer studies examining relapse prevention. Finally, there are a small number of interesting studies suggesting utility in bipolar depression. This paper will critically review available randomized clinical trials utilizing antipsychotic agents in bipolar disorder.     

Atypical antipsychotics in the treatment of bipolar disorder

Atypical antipsychotic medications are widely used for the treatment of bipolar disorder. Most empirical support suggests that these medications are efficacious in the treatment of acute mania, but there is considerably less support for the utility of these drugs in other phases of bipolar disorder. However, it is likely that several of these drugs will demonstrate efficacy in relapse prevention, and perhaps antidepressant efficacy in bipolar disorder as more studies are conducted. Atypical antipsychotics offer different side effect profiles than older antipsychotics, which may be of benefit for some patients. Consequently, atypical antipsychotics provide an important treatment option for bipolar patients.     

Valproate in the treatment of rapid-cycling bipolar disorder

Six consecutive patients with rapid-cycling bipolar disorder, refractory or only minimally responsive to treatment with lithium salts and neuroleptics, including five also refractory to carbamazepine, all demonstrated a moderate or marked response to the anticonvulsant valproate. These observations suggest that valproate may represent a promising treatment alternative in this often treatment-resistant form of bipolar disorder.     

Atypical antipsychotics in the treatment of bipolar disorder

Atypical antipsychotic medications are widely used for the treatment of bipolar disorder. Most empirical support suggests that these medications are efficacious in the treatment of acute mania, but there is considerably less support for the utility of these drugs in other phases of bipolar disorder. However, it is likely that several of these drugs will demonstrate efficacy in relapse prevention, and perhaps antidepressant efficacy in bipolar disorder as more studies are conducted. Atypical antipsychotics offer different side effect profiles than older antipsychotics, which may be of benefit for some patients. Consequently, atypical antipsychotics provide an important treatment option for bipolar patients.     

Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder

Autism is a neurodevelopmental disorder characterized by impairment in three core symptom domains: socialization, communication, and repetitive/stereotyped behaviours. Other associated symptom domains are also affected including impulsivity/aggression, self-injury, anxiety, and mood lability. Divalproex has been shown to have efficacy in treating epilepsy, bipolar disorder, mood lability, and impulsive aggression. The present study evaluated the use of divalproex in the treatment of repetitive, compulsive-like symptoms of autism spectrum disorder (ASD). Thirteen individuals with ASD participated in an 8-wk, double-blind, placebo-controlled trial of divalproex sodium vs. placebo. There was a significant group difference on improvement in repetitive behaviours as measured by the Children's Yale-Brown Obsessive Compulsive Scale (C-YBOCS) (p=0.037) and a large effect size (d=1.616). This study provides preliminary support for the use of divalproex in treating repetitive behaviours in ASD. Further research is needed to evaluate the specificity and mechanism of action of these findings.     

Asenapine for the treatment of bipolar disorder

Introduction: Bipolar I disorder (BDI) is amongst the most debilitating psychiatric conditions with a great impact on both patients and their families. A class of drugs commonly used in this condition is second-generation antipsychotics (SGAs) including asenapine, one of the latest to be introduced into the clinical practice worldwide to treat manic episodes in BDI.

Areas covered: The aim of this paper is to critically review the literature on the pharmacological characteristics, tolerability, and safety data of asenapine, as well as on its short- and long-term clinical trials in manic episodes as both a monotherapy and as an add-on treatment.

Expert opinion: The available data indicate that asenapine is an effective antimanic agent in both adult and pediatric patients and that it might also improve depressive symptoms and recurrences in BDI patients. Its tolerability profile is good, and its most common side effects are somnolence, light extrapyramidal symptoms, dizziness, weight gain, and oral (but reversible) hypoesthesia. Taken together, the published studies indicate that asenapine might be an effective therapeutic agent in BDI with a broad spectrum of clinical activities. Further double-blind, short- and long-term studies are, however, necessary to clarify its precise role in the treatment of BD.     

Levetiracetam in the treatment of rapid cycling bipolar disorder

Levetiracetam (LEV) is a novel anticonvulsant that is currently investigated in bipolar disorder. It may be useful in the treatment of refractory and complicated cases, in which conventional mood stabilizers are not effective. We report two cases of rapid cycling bipolar disorder in which the add-on of LEV to a conventional treatment regimen improved symptoms of depression, as well as those of mania/mixed mania, and disrupted the severe rapid cycling pattern.     

Special issues in the treatment of paediatric bipolar disorder

Paediatric bipolar disorder (PBD) is an increasingly diagnosed disorder affecting an estimated 1% of children and adolescents. Pharmacological treatment studies in PBD have lagged far behind those in adults. Children are currently treated with pharmacological agents, most of which have proven efficacy in adults. However, PBD is distinct from adult forms of bipolar disorder (BD) and may present unique treatment challenges. PBD often presents with rapid cycling and mixed manic states and a high co-morbidity with behavioural and attention disorders. Early onset depression may also be an early sign of PBD. Due to developmental considerations, the diagnosis of BD may be difficult to make in children without semi-structured interviews. This report discusses the special issues that should be considered when treating PBD and reviews the current literature regarding pharmacotherapy of this population. Mood stabilisers have been studied mostly in an open, uncontrolled fashion but there is growing evidence that lithium, divalproex and carbamazepine are effective in treating PBD. More recent treatment options include atypical antipsychotics and newer anticonvulsants. Other novel agents are currently being investigated in adult BD and may prove applicable to the paediatric form. Finally, based on the available data, a treatment algorithm for PBD is proposed.     

Special issues in the treatment of paediatric bipolar disorder

Paediatric bipolar disorder (PBD) is an increasingly diagnosed disorder affecting an estimated 1% of children and adolescents. Pharmacological treatment studies in PBD have lagged far behind those in adults. Children are currently treated with pharmacological agents, most of which have proven efficacy in adults. However, PBD is distinct from adult forms of bipolar disorder (BD) and may present unique treatment challenges. PBD often presents with rapid cycling and mixed manic states and a high co-morbidity with behavioural and attention disorders. Early onset depression may also be an early sign of PBD. Due to developmental considerations, the diagnosis of BD may be difficult to make in children without semi-structured interviews. This report discusses the special issues that should be considered when treating PBD and reviews the current literature regarding pharmacotherapy of this population. Mood stabilisers have been studied mostly in an open, uncontrolled fashion but there is growing evidence that lithium, divalproex and carbamazepine are effective in treating PBD. More recent treatment options include atypical antipsychotics and newer anticonvulsants. Other novel agents are currently being investigated in adult BD and may prove applicable to the paediatric form. Finally, based on the available data, a treatment algorithm for PBD is proposed.     

Concordance with treatment guidelines for bipolar disorder: data from the systematic treatment enhancement program for bipolar disorder

Background: Concordance with evidence-based guidelines in the treatment of chronic mental disorders is typically low. The study assesses the degree of concordance to recommendations of published treatment guidelines for bipolar disorder in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Potential demographic and clinical predictors of adherence were examined. Methods: STEP-BD treating psychiatrists participated in extensive training in evidence-based pharmacological management focusing on published clinical practice guidelines. Recommended medications and dosing for each specific mood episode were extracted from published treatment guidelines and collapsed into a Composite guideline. Prescribed medication information for patients at the first visit in a prospectively observed new-onset mood episode (depressive, mixed, or hypomanic/manic) was then compared with guideline recommendations. Results: The current study included 964 STEP-BD patients, observed over 2 years, who experienced a prospectively observed episode (n = 716 depressive; n = 182 hypomanic/ manic; n = 66 mixed). Guideline concordant treatments were prescribed in 81.8% of mixed episodes, 81.9% of hypomanic/manic episodes, and 83.4% of depressive episodes, exceeding rates previously reported in randomized controlled trials of guideline implementation. Younger age of onset and receipt of adequate pharmacotherapy at STEP-BD entry predicted those more likely to receive guideline-concordant care. Conclusions: The use of guideline concordant pharmacological treatments was substantially higher than reported under naturalistic conditions. We speculate that basic provider education plus a collaborative approach to medication choice may have contributed to the high treatment concordance rates in this large national trial. As in other studies, few patient-specific factors were associated with the likelihood of receiving guideline-concordant care.