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Objectives: The anterior cingulate is thought to be essentially involved in impulsivity and affect regulation and in the pathogenesis of depression as well as of attention deficit/hyperactivity disorder. At the same time alterations in glutamatergic neurotransmission in the frontal forebrain have been found in imaging studies in Attention Deficit Hyperactivity Disorder (ADHD) and in depressive patients. Therefore we hypothesized that glutamate/glutamine (Glx) signals in the anterior cingulate cortex (ACC) of depressed ADHD patients might differ from that in non-depressed patients. Methods: Fourteen male adult patients with ADHD were included into the study. Chemical Shift Imaging of ACC was performed. Subgroups were defined based on scores on the Beck Depression Inventory (BDI) and ratios of metabolites were compared between groups. Additionally correlation analyses of BDI scores with metabolite ratios were calculated. Results: Significantly lower Glx signals and N-acetyl-aspartate (NAA) signals were found in the left anterior cingulate cortex of depressed ADHD patients. The Glx/Cr and NAAX/Cr ratios in the left ACC correlated significantly with BDI-scores. Conclusions: To our knowledge this is the first report about a relationship between depressive symptoms and metabolite disturbances in ACC of adult patients with ADHD. Our preliminary data produce first evidence for a putative link between neurochemical alterations in the ACC and depressive symptoms. They should be controlled for in further studies.

ADHD is a serious risk factor for co-occurring psychiatric disorders and negative psychosocial consequences in adulthood. Previous trials on psychotherapeutic concepts for adult ADHD are based on behavioural (cognitive behavioural and dialectical behavioural) psychotherapeutic approaches and showed significant effects. The aim of our study group (COMPAS) is to carry out a first randomized and controlled multicentre study to evaluate the effects of a disorder tailored psychotherapy in adult ADHD compared to clinical management in combination with psychopharmacological treatment or placebo. A total of 448 adults with ADHD according to DSM-IV will be treated at seven university sites in Germany. In a four-arm design, patients are randomized to a manualized dialectical behavioural therapy (DBT) based group programme plus methylphenidate or placebo or clinical management plus methylphenidate or placebo with weekly sessions in the first 12 weeks and monthly sessions thereafter. Therapists are graduated psychologists or physicians. Treatment integrity is established by independent supervision. Primary endpoint (ADHD symptoms measured by the Conners Adult Rating Scale) is rated by interviewers blind to the treatment allocation. Intention-to-treat analysis will be performed within a linear regression model (Current Controlled Trials ISRCTN54096201). The trial is funded by the German Federal Ministry of Research and Education (01GV0606) and is part of the German network for the treatment of ADHD in children and adults (ADHD-NET).

Introduction: Neurobiological research has implicated the cerebellum as one possible site of neurophysiological dysfunction in ADHD. Latest theoretical conceptualizations of the cerebellum as core site of the brain to model motor as well as cognitive behavior puts further weight to the assumption that it might play a key role in ADHD pathophysiology. Methods: 30 medication free adult ADHD patients and 30 group matched (gender, age and education) healthy controls were investigated using the method of chemical shift imaging (CSI) of the cerebellum. The vermis, left and right cerebellar hemispheres were processed separately. Results: We found significantly increased glutamate-glutamine (Glx) to creatine (Cre) ratios in the left cerebellar hemisphere. No other differences in measured metabolite concentrations were observed. Discussion: To our knowledge this is the first evidence for neurochemical alterations in cerebellar neurochemistry in adult ADHD. They relate well to recent hypotheses that the cerebellum might control mental activities by internal models.

The last decade has seen an increasing interest in the method of magnet resonance spectroscopy (MRS) since this is the only research tool that allows a non-invasive in vivo assessment of neurochemical aspects of ADHD without employing ionising radiation. In this paper we review published MRS results with respect to childhood, adolescence and adult ADHD.We searched the Medline (Pub Med) database using the key words ADHD, attention-deficit/hyperactivity disorder, magnet resonance spectroscopy, MRS and spectroscopy. Citations of identified articles were also searched for relevant studies. Meta-analyses were performed for the measured metabolites and regions of assessment.Sixteen studies could be identified that used MRS to investigate the neurobiology of ADHD. Two regions could be identified as the focus of spectroscopic investigations--the frontal lobe including anterior cingulate cortex and parts of prefrontal cortex and the basal ganglia, mostly striatum, alongside the fronto-striato-thalamo-frontal circuits. As for metabolites, in the majority of studies the ratios to creatine and not absolute concentrations of metabolites were estimated. Choline compounds, N-acetyl-aspartate and glutamate/glutamine (to creatine ratios) could be identified as being altered in several studies in ADHD. The meta-analysis showed increased choline compounds in several researched regions.MRS is a promising tool for the non-invasive in vivo assessment of the cerebral neurochemistry in ADHD. More regions of interest (ROI) like amygdala, hippocampus, thalamus and cerebellum should be assessed in future studies. Further methodological improvements of MRS are desirable in order to assess the absolute metabolite concentration of several ROIs at the same time. Such developments will open novel perspectives in spectroscopic investigations of ADHD.

BackgroundTo date, nearly all research of subtype differences in ADHD has been performed in children and only two studies, with conflicting results, have covered this subject in adults with ADHD.ObjectiveThis study examined subtype differences in the clinical presentation of ADHD-symptoms, related psychopathological features, psychosocial functioning and comorbid psychiatric disorders in adults with ADHD.MethodOne hundred and eighteen adults with ADHD, diagnosed according to DSM-IV criteria, and a population based control group underwent diagnostic evaluations with clinical interviews for ADHD, DSM-IV disorders and demographic features. Comparisons were made between ADHD combined type (n = 64), predominantly inattentive type (n = 30) and predominantly inattentive type, anamnestically combined type (n = 24), relative to each other and to a community control group (n = 70).ResultsThe four groups did not differ in age and gender composition. All ADHD groups had significantly less education, were significantly more often unemployed and reported significantly more lifetime psychiatric comorbidity than controls. In comparison to each other, the three ADHD groups differed mainly in core symptoms and the pattern of comorbid psychiatric disorders, whereas no prominent differences in associated psychopathological features and most of the assessed psychosocial functions could be found. Patients with ADHD combined type and inattentive, anamnestically combined type both presented with significantly more hyperactive symptoms and also showed more impulsive symptoms than those with the predominantly inattentive type. With a similar overall lifetime psychiatric comorbidity in the three groups, patients with ADHD combined type and inattentive, anamnestically combined type suffered significantly more from lifetime substance use disorders than patients with predominantly inattentive type.ConclusionOur results clearly show impaired psychosocial adjustment and elevated risk for additional psychiatric disorders in adults with all subtypes of ADHD, compared to healthy controls. They provide preliminary evidence that in adult ADHD there might be a subgroup of patients, which is classified as predominantly inattentive subtype according to current diagnostic criteria, but which in its clinical presentation is in between ADHD combined and inattentive type. Further studies are needed to evaluate this finding and to gain a clear picture of its validity.

In order to detect possible links between structural and neurochemical brain abnormalities we applied high resolution morphometric imaging and short-echo time absolute-quantification magnetic resonance spectroscopy (MRS) at the left hand side to the amygdala in 12 patients with borderline personality disorder (BPD) and 10 group-matched healthy controls. Confirming earlier reports we found a significant 11-17% reduction of amygdalar volumes in patients with BPD. In addition there was a significant 17% increase of left amygdalar creatine concentrations in BPD patients. Left amygdalar creatine concentration correlated positively with measures of anxiety and negatively with amygdalar volume. This pilot study of simultaneous amygdalar morphometry and spectroscopy in BPD reveals a possible link between amygdalar volume loss, psychopathology and neurochemical abnormalities in terms of creatine signals.

Subtle prefrontal and limbic structural abnormalities have been reported in borderline personality disorder (BPD). In order to further validate the previously reported findings and to more precisely describe the nature of the structural change we performed a voxel-based morphometric (VBM) study in patients with BPD. Twenty female patients with BPD and 21 female healthy controls were investigated. High-resolution 3-D datasets were acquired and analyzed following an optimized protocol of VBM in the framework of statistical parametric mapping (SPM99). Gray matter volume loss was found in the left amygdala. No other differences in gray or white matter volume or density were found anywhere else in the brain. Our findings support the hypothesis that temporolimbic abnormalities play a role in the pathophysiology of BPD. Prefrontal structural alterations in BPD were not observed in this study.

Background Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. Methods Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. Results We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. Conclusions While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.

Ten male patients with type I alcohol dependency fulfilling DSM-IV criteria for alcohol dependency were investigated twice using IBZM-SPECT after alcohol withdrawal (day 2 and day 28 after withdrawal). Five patients had a history of physical withdrawal symptoms, 5 patients had no such history. The group with physical withdrawal symptoms showed higher IBZM binding in both scans indicating differences of dopaminergic neurotransmission in different subtypes of alcohol dependency.

The authors examined the brains of patients with borderline personality disorder (BPD) by using short echo time single voxel spectroscopy and found a significant 19% reduction of absolute N-acetylaspartate concentrations in the dorsolateral prefrontal cortex in BPD (P=0.01) compared with control subjects.

Fast alle Psychopharmaka werden durch die Cytochrom-P450-Enzyme der Leber abgebaut. Beim Menschen sind mindestens 5 Isoenzyme fur diesen Prozes verantwortlich. Diese konnen in jeweils unterschiedlichem Umfang durch eine Reihe von Medikamenten in ihrer Aktivitat beeinflust werden. Bei gleichzeitiger Anwendung mehrerer Substanzen kann es durch diesen Mechanismus zu Wechselwirkungen mit potentiell ernsten Folgen kommen. So inhibieren die meisten der selektiven Serotonin-Wiederaufnahmehemmer P450-Enzyme und konnen dadurch z.B. die Plasmakonzentrationen von trizyklischen Antidepressiva in toxische Bereiche heben. Carbamazepin hingegen induziert viele der Isoenzyme; durch den schnelleren Abbau von Trizyklika oder Neuroleptika konnen zu geringe Konzentrationen dieser Substanzen resultieren und Rezidive von Depressionen oder Psychosen ausgelost werden. Uberdies weisen aufgrund eines genetischen Polymorphismus 5–10% der Bevolkerung eine geringere Aktivitat des Isoenzyms CYP2D6 auf und reagieren deshalb mit verstarkten Nebenwirkungen auf ubliche Dosierungen vieler Pharmaka. In dieser Ubersichtsarbeit wird systematisch auf pharmakokinetische Interaktionen im Bereich der Psychopharmakologie hingewiesen, die bisher berichtet wurden oder zu befurchten sind. Besonderer Wert wird dabei auf die klinische Signifikanz solcher Ergebnisse gelegt.

Very few controlled clinical trials have been assessing the interaction of antipsychotics and antiepileptics. However, schizophrenic patients frequently receive a combination therapy consisting of haloperidol and carbamazepine. The data for this treatment strategy are contradictory and may depend on the initial plasma concentration of the antipsychotic. There is convincing evidence that after addition of carbamazepine the plasma concentration of neuroleptics drops due to hepatic enzyme induction. In this study, we treated 18 schizophrenic patients either with haloperidol alone or in combination with carbamazepine. The use of carbamazepine was associated with a dramatic fall in haloperidol plasma levels and a worse clinical outcome compared to the monotherapy group. These results, together with a review of the literature, lead us to the conclusion that there are no obvious advantages of carbamazepine co-medication in schizophrenia compared to an optimized neuroleptic monotherapy.

1. 1. The patient, a 59 year old woman, developped a state of acute excitation several hours after the administration of 400 mg of the fluorquinolone pefloxacin in combination with 1000 mg paracetamol. Nine days later, after a total dosage of pefloxacin of 800 mg, she was admitted to our hospital with a psychotic disorder. 2. 2. There was a full remission of symptoms after treatment with perazine up to a dosage of 500 mg/day. 3. 3. Three years ago. the patient had developped a manic state under a medication with corticosteroids. 4. 4. So far. the mechanism of — in this case — long-lasting central nervous side effects of fluorquinolones is not known. In patients with increased vulnerability of the CNS or in advanced age the application of fluorquinolones should be considered critically, in particular in combination with non-steroidal antiinflammatory drugs.

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in childhood and adolescence and in a considerable number of patients it persists into adulthood. A network of brain regions have been shown to be abnormal in ADHD. In the present study we used magnetic resonance volumetry to investigate a possible role of the orbitofrontal cortex (OFC). Eight never medicated male patients fulfilling diagnostic criteria for ADHD and 17 male healthy controls were investigated. There was a significant reduction of the volume of the left OFC in patients with ADHD. It remains unknown whether small volumes are a primary deficit or a result of dysfunctional activation during childhood in terms of a residual deficit or a specific type of adult outcome of the disease.

In contrast to the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents, few disorder-oriented psychotherapeutic approaches are currently available for the treatmen

Attention-deficit hyperactivity disorder (ADHD) in adulthood is a serious health problem with a prevalence of up to 4%. Limbic structures have been implicated in the genesis of ADHD; it has been suggested that they mediate mood and cognitive disturbances in affected individuals. Recently, a large study involving children and adolescents with ADHD reported bilateral enlargement of the hippocampus and indirect evidence of amygdala volume loss in this patient sample. We sought to test the hypothesis that, like in pediatric patients, there might be hippocampus and amygdala volume abnormalities in adult patients with ADHD.We studied 27 adult patients with ADHD and 27 group-matched healthy volunteers using a 1.5 T magnetic resonance imaging scanner. We manually obtained morphometric measurements of the regions mentioned.In contrast to previous findings in children and adolescents, we found no significant differences in hippocampus and amygdala volumes among adults with and without the disorder.Findings of hippocampus enlargement and amygdala volume loss are not very stable across different samples of patients with ADHD. Contradictory findings may be related to the different locations of alterations along the complex circuits responsible for the different symptoms of ADHD. Further studies involving larger samples of adult patients with ADHD and using multimodal designs are needed.

Until the late 1990s, attention deficit hyperactivity disorder (ADHD) was often regarded in the German speaking countries as a disorder affecting only children and adolescents and which fades away with the onset of adulthood. Research has shown, however, that ADHD frequently persists into adulthood and is a relevant differential diagnosis for many psychiatric disorders (1–3). A factor of particular importance for family medicine is the high genetic penetrance of ADHD. In the majority of cases several generations of a family are affected.

Attention deficit hyperactivity disorder (ADHD) is a serious mental disorder that often persists in adulthood. In a pilot study, a structured skills training group program for adult ADHD led to significant symptomatic improvements. The present study evaluated the program's effectiveness, feasibility, and patient acceptability in a multicenter setting. Seventy-two adult ADHD patients were assigned to 13 two-hour weekly sessions at 4 different therapy sites. The therapy was well tolerated and led to significant improvements of ADHD, depressive symptoms, and personal health status (p < 0.001). The factors treatment site and medication did not contribute to the overall improvement. Patients regarded the program topics "behavioral analyses," "mindfulness," and "emotion regulation" as the most helpful. In this multicenter study, the therapy program showed therapist-independent effects and seemed to be disorder-specific. This warrants the effort of organizing further controlled studies.

Until the late nineties, attention deficit and hyperactivity disorder (ADHD) was often regarded in Germany as a disorder that fades away in late adolescence. However, it has recently become clear from numerous studies that core symptoms of ADHD persist into adulthood in a substantial subgroup of patients.Selective review of relevant literature in Medline, up to September 2007.The prevalence of ADHD in adulthood is estimated at about 2%. Core symptoms include attention deficit in the presence of understimulation, chronic restlessness, impulsivity, disorganized behaviour, and disorders of affect regulation. The extent of psychosocial impairment depends on symptom severity, psychiatric comorbidity (such as addiction or depression), and psychosocial support. As in childhood, ADHD in adulthood is a clinical diagnosis. Genetic factors probably play a key role in primary ADHD. Treatment should include psychotherapy and medical treatment.ADHD in adulthood is commoner than for example bipolar disorder or schizophrenia. It may be regarded as a risk factor for the development of other psychiatric conditions. Highly effective treatment is possible not only in childhood but also in adulthood. The problem of off-label use of psychotropic medication in adults limits treatment in adult ADHD.

Background The dopaminergic system is thought to be essentially involved in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). However, there is also evidence for abnormalities in the glutamatergic system and recent theories focus on a disturbed interaction between the two systems as the essential pathogenetic mechanism of ADHD. In the present study, we wanted to test the hypothesis that prefrontal glutamate signals indirectly indicate dopaminergic dysfunction in adult patients with ADHD. Methods Twenty-eight adult patients with ADHD and 28 group-matched healthy volunteers were studied clinically and using chemical-shift MR spectroscopy (MRS) of the prefrontal cortex covering the anterior cingulate gyrus. Results A significant reduction of the combined glutamate/glutamine to creatine ratio in the right anterior cingulate cortex in patients with ADHD was found. Discussion Glutamatergic alterations as measured with MRS might play a role in the pathogenesis of adult patients with ADHD.

We report the case of a patient developing psychosis after the addition of mirtazapine, a novel antidepressant enhancing serotonergic neurotransmission, to a chronic levodopa regimen. There was complete and rapid recovery upon low-dose clozapine treatment. To our knowledge, this is the first published case of a mirtazapine-levodopa interaction and the second case report of a psychosis induced by a serotonergic antidepressant in a patient with Parkinson's disease (PD). This phenomenon might be due to a postsynaptic serotonin receptor supersensitization caused by low central serotonin levels in treated PD.

Study Objectives: Previous studies in children with attention-deficit/hyperactivity disorder and attention deficit disorder (ADHD/ADD) have shown impaired sleep quality with increased nocturnal motor activity. However, polysomnographic findings are not unequivocal. Up to now, in adults with ADHD, only 1 case-control polysomnographic study with small sample size has been performed. We investigated objective and subjective sleep quality in adult ADHD, including an electroencephalogram spectral power analysis. Design: Single-blind comparative study. Setting: University medical center. Participants: Twenty adult unmedicated ADHD patients without current comorbid major depression, drug abuse, or comorbid axis-ll disorder and 20 sex- and age-matched control subjects. Interventions: N/A. Measurements: Conventional polysomnographic parameters and sleep electroencephalogram spectral power analysis was calculated for the 2 laboratory nights. Subjective sleep parameters were estimated by sleep questionnaires to assess the relationship between objective and subjective sleep measurements. Results: Adult ADHD patients showed increased nocturnal motor activity (as indicated by heightened indexes of periodic leg movements in sleep), which was significantly inversely correlated with subjective total sleep time. Although ADHD patients displayed significantly increased objective total sleep time, the subjective ratings documented impaired sleep quality in those with ADHD. Other polysomnographic sleep patterns and spectral electroencephalogram parameters did not differ between ADHD patients and normal controls. Conclusions: Similar to children, adults with ADHD show increased nocturnal motor activity. Otherwise, sleep does not seem to be impaired in ADHD patients. However, the dissociation between objective and subjective sleep parameters points to a misinterpretation of sleep quality in patients with ADHD.

There are some reports in the literature about the comorbidity of Darier's Disease (keratosis follicularis) and psychiatric illness (e.g. mental retardation or affective disorders). Here we present evidence that schizophreniform psychosis may also be associated with Darier's Disease.

The new antiepileptic lamotrigine has been shown to be effective in the treatment of focal epilepsies with or without secondary generalization and has also been suggested to be efficacious in the treatment and prophylaxis of affective disorders. Therefore, we analyzed its possible benefit in a patient with refractory bipolar affective disorder. Lamotrigine (up to 150 mg/d) was added to valproate (2700 mg/d), substituting previously administered neuroleptics. A considerable improvement of the patient's condition was achieved several days after the beginning of lamotrigine co-administration, and lasted over the total follow-up period of more than one year. The plasma concentrations after total remission were in the range of 1.9 to 6.2 mg/l for lamotrigine and 57.1 to 95.2 mg/l for valproate. This positive action of lamotrigine is discussed in the context of the drug's elementary effects on sodium and calcium channels.

Attention deficit hyperactivity disorder (ADHD) is a severe and often debilitating mental disorder, which begins in childhood and can persist into adulthood. Both major classificatory systems, ICD-10 and DSM-IV, include the age-of-onset criterion (AOC) requiring clinically relevant symptoms before the age of 7 years. In clinical practice, particularly in adult psychiatry, it is often difficult to establish this AOC when ADHD remained unrecognized in childhood. In the literature, there is controversy about the validity of this criterion. In order to explore the validity of the AOC, we performed a retrospective study in adult patients with ADHD. Fifty consecutively diagnosed patients were subjected to a standardized diagnostic procedure. Depending on the onset of clinical symptoms, patients were divided in an early onset and in a late onset ADHD subgroup. Fourteen patients (28%) described late onset ADHD. In four of these patients (8% of the total sample), this assessment was confirmed by parent ratings. There was no difference between early onset and late onset ADHD groups in terms of psychopathology or psychiatric comorbidity.

Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder.Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls.We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes.While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.

The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [(18)F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [(18)F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD.

Objective: Clinical and epidemiological observations and neurobiological data suggest that there might be an inherent link between attention deficit hyperactivity disorder (ADHD) and recurrent brief depression (RBD). In this psychopathological study, we investigated the comorbidity between these two conditions. Method: Using an index patient approach 40 adult out-patients fulfilling the criteria for ADHD were investigated for lifetime history of RBD and another 40 out-patients with the primary diagnosis of RBD were investigated for a lifetime history of ADHD. Results: We found a high prevalence of RBD in patients with ADHD (70%) while the prevalence of ADHD in the index sample with RBD was smaller (about 40%). Conclusion: In terms of comorbidity ADHD was the second commonest psychiatric disorder in patients with RBD next to other affective disorders. The psychopathological pattern of lifetime comorbidity might be of clinical relevance in terms of medical treatment.

This report focuses on a case of major depression and panic disorder after heart transplantation. Due to these disorders, the male patient's compliance with cardiological treatment became increasingly insufficient. There are no controlled studies on psychopharmacological opportunities in cases such as this one. The patient was treated with sertraline and the outcome was healthy, without cardiovascular adverse effects or drug-drug interactions.

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.

1. This is a report of a patient who developed an acute organic psychosis due to neurotoxicity of lithium several days after tapering off a long-lasting clozapine therapy. 2. The organic brain syndrome with initial illusionary misperceptions, a confusional state and a lapse into a pre-coma developed three days after the end of clozapine therapy and seven days after the beginning of haloperidol addition. 3. Possible pharmacokinetic and pharmacodynamic factors responsible for the severe neurotoxicity of lithium after withdrawal of clozapine and addition of haloperidol are discussed.