Joerg Walden

Incidence of childhood-onset bipolar illness in the USA and Europe

The relative incidence of childhood-onset bipolar illness in the USA compared with that in Europe is controversial. We examined this issue in more than 500 out-patients (average age 42 years) with bipolar illness who reported age at onset of first episode, family history, and childhood physical or sexual abuse. Childhood or adolescent onset of bipolar illness was reported by 61% of those in the US cohort but by only 30% of those in The Netherlands or Germany. In the USA there was also twice the incidence of childhood adversity and genetic/familial risk for affective disorder. The findings deserve replication and further exploration.

Effects of carbamazepine and valproate on haloperidol plasma levels and on psychopathologic outcome in schizophrenic patients.

The objective of this study was to compare the effects of carbamazepine (CBZ) and valproate (VPA) cotreatment on the plasma levels of haloperidol and on the psychopathologic outcome in schizophrenic disorders. In this controlled clinical trial, 27 patients with an ICD-10 diagnosis of schizophrenia (N = 24) or schizoaffective disorder (N = 3) were randomly assigned to receive 4 weeks of treatment with either haloperidol alone, haloperidol with CBZ, or haloperidol with VPA. Whereas the haloperidol dose remained stable, the antiepileptic drug doses were adjusted to achieve therapeutic plasma levels. Clinical state was rated by the Positive subscale of the Positive and Negative Syndrome Scale and the Inpatient Multidimensional Psychiatric Scale. The use of CBZ was associated with significantly lower haloperidol plasma levels and with a worse clinical outcome compared with antipsychotic monotherapy. VPA had no significant effect on either plasma levels or on psychopathology. Our results suggest that comedication with haloperidol and CBZ is associated with a high risk for treatment failure. This might be a result of a pharmacokinetic interaction on the hepatic level. The concomitant use of VPA with neuroleptic therapy is not impaired by clinically significant drug interactions, but it is not associated with a better outcome under our conditions.

Differential clinical characteristics, medication usage, and treatment response of bipolar disorder in the US versus The Netherlands and Germany

Increased early-onset bipolar illness was seen in the US compared with the Netherlands and Germany (abbreviated here as Europe), but other clinical characteristics, medication use, and treatment response have not been systematically explored. Outpatients with bipolar disorder were treated naturalistically and followed prospectively at four sites in the US and three in Europe. Data and clinical characteristics were collected from patient questionnaires, and medication usage and good-to-excellent response to treatment for at least 6 months ascertained from daily clinician ratings on the National Institutes of Mental Health-Life Chart Method. Almost all clinical characteristics earlier associated with a poor treatment response were more prevalent in the US than in Europe, including early onset, environmental adversity, rapid cycling, more than 20 prior episodes, comorbid anxiety and substance abuse disorders, and a positive parental history for an affective disorder. Lithium was used more frequently in Europe than in the US and had a higher rate of success, whereas valproate was used more in the US, with a trend toward higher success in Europe. Antidepressants were used more in the US, but had extremely low success rates. Many other agents were deployed differently on the two continents, but success rates were consistently lower in the US than in Europe. In conclusion, clinical characteristics and patterns of medication usage and effectiveness differed markedly in the two continents suggesting the need for uncovering explanations and considering the two populations as heterogeneous in the future pharmacological studies.

Efficacy of Quetiapine Monotherapy in Rapid-Cycling Bipolar Disorder in Comparison With Sodium Valproate

Background: Rapid-cycling bipolar disorder is often characterized by a lack of response to psychopharmacological treatment, and a standard therapy has not been developed yet. The aim of this study was to examine the long-term efficacy and safety of a monotherapy with quetiapine or sodium valproate (VPA) in patients with rapid-cycling bipolar disorder. Methods: This open-label, randomized, parallel group monotherapy pilot study was conducted at 3 German centers. A sample of 38 remitted or partly remitted patients with bipolar disorder and rapid cycling (quetiapine n = 22; VPA n = 16) were treated with quetiapine or VPA (flexible dose design) for 12 months. Results: Forty-one percent of the patients with quetiapine and 50% with VPA completed the trial. On the basis of ITT-LOCF, Life Chart Method data showed that patients being treated with quetiapine had significantly less moderate to severe depressive days than patients on VPA (mean ± SD, 11.7 ± 16.9 days vs 27.7 ± 24.9 days; P = 0.04) while they did not differ in the number of days with manic or hypomanic symptoms. Furthermore, according to the Clinical Global Impression Scale, bipolar version, the responder rates tended to be higher for quetiapine than for VPA. There were no differences found evaluating the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Scale, and the Young Mania Rating Scale. The incidence of adverse events, especially of orthostatic dysregulation, sedation, and weight gain, was significantly higher in the quetiapine group. Conclusions: In this study, quetiapine was more effective than VPA on the number of depressive days and similar to VPA in the treatment of manic symptoms. Quetiapine was associated with a greater incidence of side effects, particularly orthostatic dysregulation, sedation, and weight gain.

Modulation of Neural Cell Membrane Conductance by the Herbal Anxiolytic and Antiepileptic Drug Aswal

To evaluate the effects of aswal on ionic fluxes and neuronal excitation, we performed extracellular and whole cell patch clamp recordings on CA1 pyramidal neurons of guinea pigs and Long-Evans rats. Aswal (100– 250 mg/l) was administered systemically, and its effects on the rate of synchronized extracellular field potentials (EFP), membrane parameters, action potentials and postsynaptic potentials were recorded. The extracellular results obtained are consistent with calcium antagonistic properties. Intracellular recordings suggest that a direct sodium antagonistic effect as seen in many antiepileptic drugs plays no significant role. Further effects on ligand gated ion channels are discussed controversially. In summary, the cellular action of aswal appears heterogeneous with calcium antagonism playing a prominent role in counteracting excitation which may be a common feature in epilepsy and different psychiatric conditions as mood and anxiety disorder.

Bupropion-induced isolated impairment of sensory trigeminal nerve function

Bupropion is increasingly used for nicotine withdrawal and in the treatment of major depression, especially in bipolar patients. We present the case of a 38-year-old female schizoaffective, rapid-cycling patient treated with bupropion for a depressive episode. After 4 weeks of successful treatment (300 mg/day), the patient developed a circumscribed unilateral impairment of sensory trigeminal nerve function. Symptoms completely recovered after discontinuation of bupropion. When re-exposed to bupropion, mild symptoms reappeared, leading to final discontinuation of bupropion. With this natural on-off-on-off design, a causative role of bupropion for trigeminal impairment in this patient can be assumed. To our knowledge, a similar side-effect of bupropion has not been described to date.