Pharmacopsychiatry (Pharmacopsychiatry)

Publications in this journal

• Article: Dopamine-Modulated Aversive Emotion Processing Fails in Alcohol-Dependent Patients.

  T Kienast, F Schlagenhauf, M A Rapp, J Wrase, I Daig, H-G Buchholz, M N Smolka, G Gründer, Y Kumakura, P Cumming, K Charlet, P Bartenstein, A R Hariri, A Heinz
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  ABSTRACT: Negative mood states after alcohol detoxification may enhance the relapse risk. As recently shown in healthy volunteers, dopamine storage capacity (V d) in the left amygdala was positively correlated with functional activation in the left amygdala and anterior cingulate cortex (ACC) during an emotional task; high functional connectivity between the amygdala and the ACC, a region important for emotion regulation, was associated with low trait anxiety. Based on these findings, we now tested whether detoxified alcohol-dependent patients have a disrupted modulation of the anterior cingulate cortex activation in response to aversive stimuli by amygdala dopamine. Furthermore, we asked whether disrupted functional coupling between amygdala and ACC during aversive processing is related to trait anxiety.We used combined 6-[18F]-fluoro-l-DOPA positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and Spielberger's state-trait anxiety questionnaire (STAI) in 11 male detoxified alcohol-dependent patients compared to 13 matched healthy controls.Unlike healthy controls, patients showed no significant correlation between our PET metric for dopamine storage capacity (FDOPA V d), in left amygdala and activation in left ACC. Moreover, the functional connectivity between amygdala and ACC during processing of aversive emotional stimuli was reduced in patients. Voxel-based morphometry did not reveal any discernible group differences in amygdala volume.These results suggest that dopamine-modulated corticolimbic circuit function is important for responding to emotional information such that apparent functional deficits in this neuromodulatory circuitry may contribute to trait anxiety in alcohol-dependent patients.
  Pharmacopsychiatry 01/2013;
• Article: Parental Perceived Benefits of OROS-Methylphenidate Treatment for the Child with Attention-Deficit/Hyperactivity Disorder and for Parents Themselves.

  J-W Kim, S Park, B-N Kim, M-S Shin, S-C Cho, J-H Kim, J-W Son, Y-M Shin, U-S Chung, D-H Han
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  ABSTRACT: Given the shortage of studies on parental perceived benefits of OROS-methylphenidate treatment in Asian populations, we assessed parental response to OROS-methylphenidate treatment of Korean children with attention-deficit/hyperactivity disorder (ADHD), in relation to children's academic performance and behavioral symptoms as well as parental rearing stress and depressive symptoms.We enrolled 132 medication-naïve children with ADHD into a multicenter, open-label, 12-week trial of OROS-MPH. The outcome measures were the ADHD rating scale-IV (ADHD-RS), the comprehensive attention test and academic performance rating scale, and the clinical global impression (CGI)-severity/improvement instrument (for the children) and Beck depression inventory and parenting stress index (for their parents).We found parent-perceived improvements in children's ADHD-related behavioral symptoms and academic function and their parents' depressive symptoms and parenting stress. Investigator-rated ADHD symptoms and subjects' neuropsychological function were also improved (p<0.001).Parents of Korean children with ADHD perceive that OROS-methylphenidate treatment improves their children's academic function and behavior as well as their own child-rearing stress and emotional state. These findings must be interpreted with caution, due to a non-comparative open-label trial.
  Pharmacopsychiatry 01/2013;
• Article: Association of Ethnicity with Antipsychotic Dosage Using STRUCTURE Analysis.

  A Hassan, C Teo, J L Kennedy, A Ravindran, V De Luca
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  ABSTRACT: Several studies have examined whether ethnicity as an independent factor can influence the individual's dosage of antipsychotics. However, there has been inconsistency in the results of these studies, particularly between white and non-white populations. This retrospective study tests the hypothesis of different dosing of antipsychotics in white Europeans vs. non-white Europeans considering both the self-reported ethnicity and the geographical ancestry calculated using 196 DNA markers.We collected self-reported ethnicity and DNA samples from 209 schizophrenia patients. We tested the association between self-reported and genetically-determined ethnicity with the chlorpromazine equivalent dose of each antipsychotic prescribed at the time of the assessment.We did not find any significant difference between self-reported white European -ethnicity and chlorpromazine equivalent doses (p=0.972). Furthermore, when we considered the geographical ancestry determined by the 196 SNPs, we could not find any correlation between the European ancestry and chlorpromazine equivalent dose.Our preliminary analysis shows that there is no evidence that different ethnic groups receive different dose of antipsychotics.
  Pharmacopsychiatry 01/2013;
• Article: Bispectral Index Monitoring and Seizure Quality Optimization in Electroconvulsive Therapy.

  L Kranaster, C Hoyer, C Janke, A Sartorius
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  ABSTRACT: In ECT, the relative timing of seizure induction and anesthesia may critically impact on seizure quality when anesthetic agents with anticonvulsive properties such as barbiturates or propofol are used. Measuring the depth of anesthesia by bispectral index (BIS) monitoring and thereby identifying the optimal moment for seizure induction might enhance seizure quality.Seizures from 869 individual ECT -sessions with thiopental anesthetic from 118 patients were examined in this retrospective study. The associations of the BIS value at the moment of seizure induction with 7 established seizure parameters and with a novel model of seizure quality were tested by regression analyses.BIS value at induction correlated positively with seizure duration, central inhibition, coherence and maximal heart rate, but not with midictal amplitude. Higher seizure quality was related with a higher BIS value at the moment of seizure induction.The BIS value at seizure induction serves as an independent predictor of seizure quality, influencing most other established markers. BIS monitoring appears as a simple tool to identify the optimal moment for seizure induction.
  Pharmacopsychiatry 01/2013;
• Article: Withdrawal and Discontinuation Phenomena Associated with Tranylcypromine: A Systematic Review.

  M Gahr, C Schönfeldt-Lecuona, M A Kölle, R W Freudenmann
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  ABSTRACT: Tranylcypromine (TCP) is an effective antidepressant with a complex pharmacological profile and a relevant risk of abuse and dependence. Withdrawal phenomena (WP, in the case of TCP-abuse/dependence) or discontinuation phenomena (DP, in the case of absent TCP-abuse/dependence) subsequent to abrupt termination of TCP are a potentially severe clinical syndrome. We conducted a systematic review of all previously published WP/DP cases following abrupt termination of TCP in order to identify typical clinical presentations and risk factors of WP/DP and frequency of TCP abuse or dependence within these patients. By searching the Medline and Scopus databases we identified n=25 cases (cohort WP: n=18, cohort DP: n=7). Delirium was found in n=13 patients (cohort WP: 10/55.6%; cohort DP: 3/42.9%), n=6 demonstrated WP/DP without delirium (WP: 6/33.3%; DP: 0/0%) and n=5 rapid relapse in depression (WP: 1/5.6%; DP: 4/57.1%). Mean time until development of WP/DP was 1.9 (WP) and 2.2 (DP) days. Mean duration of WP/DP was 5.7 (WP) and 11.3 (DP) days. All patients of cohort WP were described to feature TCP-abuse/dependence. Patients with delirium were on average older (41.8 years vs. 37.8 years) and featured higher mean prescribed (71.0 mg vs. 38.3 mg) and actually taken daily TCP dosages (285.8 mg vs. 187.7 mg). In conclusion, even termination of lower daily dosages of TCP may result in delirium. Thrombocytopenia features diagnostic value in patients with deliria of unknown etiology. TCP should be administered with great care, especially in dependence-prone patients.·
  Pharmacopsychiatry 01/2013;
• Article: The Influence of the Tricyclic Antidepressant Amitriptyline on Periodic Limb Movements during Sleep.

  M Goerke, A Rodenbeck, S Cohrs, D Kunz
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  ABSTRACT: Many antidepressants are associated with periodic limb movements (PLM) during sleep. Although some tricyclic antidepressants, such as amitriptyline, promote sleep and are thus often prescribed as a treatment for sleep disturbances that can accompany depression, it remains unclear whether amitriptyline is associated with PLM.32 healthy males (18-39 years) spent 2 consecutive nights in the sleep lab for polysomnographic recording. During the second night, they received either 75 mg amitriptyline or placebo in a randomized, double-blind, placebo-controlled manner.In subjects receiving amitriptyline but not in subjects receiving placebo, the number of periodic leg movements per h was significantly increased from baseline to intervention night. However, objective polysomnographic sleep parameters (such as the number of awakenings, wake after sleep onset, and sleep efficiency) and subjective sleep perception were not significantly associated with any PLM indices.Our findings indicate that amitriptyline can induce or even increase the number of PLM during sleep in healthy subjects. When treating sleep disturbances with amitriptyline, PLM should be considered as a possible cause of insufficient improvement.
  Pharmacopsychiatry 01/2013;
• Article: Predicting a 'Combined Treatment Outcome' in Chronic Schizophrenia: The Role of Demographics, Symptomatology, Functioning and Subjective -Well-being.

  D Naber, S Kollack-Walker, J Chen, V L Stauffer, B J Kinon, M Case, H Ascher-Svanum, S Kapur, J M Kane
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  ABSTRACT: The aim of this study was to determine what variables predict a 'combined treatment outcome' (COMBOUT) in patients with chronic schizophrenia.This analysis (n=522) was based on a randomized, double-blind, flexible-dose, 12-week study that enrolled chronically-ill patients diagnosed with schizophrenia or a related disorder. COMBOUT was assessed using the PANSS for symptoms, CGI-S for overall clinical status, MADRS for depressive symptoms, QLS for functioning/QOL, and SWN-K for subjective well-being. Possible predictors included demographics as well as baseline scores (Model I), and early change (week 2) scores (Model II).Model I: significantly better outcome (higher COMBOUT score) was observed in patients with lower MADRS (T= - 6.36; p<0.001) or higher QLS (T=5.05; p<0.001) scores at baseline. Model II: significantly better COMBOUT was observed in patients with early improvement of QLS (T=4.93; p<0.001), SWN-K (T=3.88; p<0.001), PANSS (T= - 2.32; p=0.021) and CGI-S scores (T= - 2.22; p=0.027). Changes in EPS were not predictors of COMBOUT in the models tested.COMBOUT at endpoint was predicted by lower depressive symptom score and higher QOL at baseline and by early improvement in psychopathology, quality of life and subjective well-being.
  Pharmacopsychiatry 01/2013;
• Article: Safety, Effectiveness and Tolerance of Buprenorphine-Naloxone in the Treatment of Opioid Dependence: Results from a Nationwide Non-Interventional Study in Routine Care.

  S M Apelt, N Scherbaum, J Gölz, M Backmund, M Soyka
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  ABSTRACT: Buprenorphine is well known in the treatment of opioid dependence. Despite a high safety profile and good tolerance buprenorphine has been subject to misuse and diversion. To reduce misuse the antagonist naloxone was added and the 4:1 combination of buprenorphine-naloxone was launched in Germany in March 2007. On the basis of the results from international clinical trials a non-interventional study was conducted to gather data on safety, effectiveness, retention and acceptability of buprenorphine-naloxone in the treatment of opioid dependent patients in routine care.A nationwide multicentre 12-month prospective, non-interventional, post-marketing, surveillance study was carried out with 12 assessment points in N=384 opioid dependent patients currently in maintenance treatment from N=69 general practitioners, clinics and outpatient clinics in Germany.N=337 data sets were eligible for analysis. The rates of patients with serious and non-serious adverse events were low with 1.2% and 17.5%, respectively. No deaths occurred during the observational period and only one hospitalization was documented. Concomitant drug use decreased for all illicit substances. Mental health and quality of life measured with standardized self-assessment questionnaires improved significantly. The 12-month retention rate was 57.1%. Of the n=181 patients still in treatment at the end of the observation period, 96.7% continued treatment with buprenorphine-naloxone.The findings of the non-interventional study indicate high effectiveness and safety of buprenorphine-naloxone in the treatment of opioid dependence. The medication was well accepted by opioid dependent patients in long-term substitution treatment with substantial reductions of concomitant drug use and measurable improvement in quality of life.
  Pharmacopsychiatry 01/2013;
• Article: A. Háber * MD, O. Rideg **, P. Osváth MD PhD***, S. Fekete MD PhD***, F. Szücs *PharmD, G.L. Kovács **MD PhD DsC, Zs. Pótó****, L. Botz No increased frequency of CYP2D6 allele duplication found in patients with ’difficult-to-treat’ depression. A pilot study Pharmacopsychiatry, accepted (IF: 2.07) http://mc.manuscriptcentral.com/pharmacopsychiatry The manuscript ID is: PHP-2012-09-0194.R2

  A. Háber * MD, O. Rideg, P. Osváth MD PhD, S. Fekete MD PhD, F. Szücs *PharmD, G.L. Kovács **MD PhD DsC, Zs. Pótó, L. Botz
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  ABSTRACT: Background: Insufficient response to antidepressant treatment may result from several factors including altered drug metabolism, thus CYP2D6 genotyping may help to assess the possible contributing factors to difficult-to-treat depression. The aim of the study was to investigate the frequency of the variant CYP2D6 alleles and the prevalence of predicted CYP2D6 phenotypes in patients with difficult-to-treat depression and compare them to the data reported in the Hungarian population. Methods: 55 patients with documented failure of at least two adequate trials of different CYP2D6-dependent antidepressants were selected for genotyping with AmpliChip CYP450 test. Results: No significant differences in CYP2D6 allele frequencies and predicted phenotype distribution could be identified in patients with difficult-to-treat depression comparing to healthy Hungarians. Limitations: Small sample size, lack of phenotyping and therapeutic drug monitoring data. Conclusions: There is a little evidence to support CYP2D6 genotyping as a routine screening but it may be a useful additional diagnostic tool in individual cases.
  Pharmacopsychiatry 01/2013;
• Article: Priorities, Satisfaction and Treatment Goals in Psychosis Patients: An Online Consumer's Survey.

  B Sterk, I Winter van Rossum, M Muis, L de Haan
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  ABSTRACT: An insight into preferences, satisfaction and treatment goals of patients is important for reaching treatment alliance and may increase the success of initiated treatment.Participants from the Netherlands, with at least one psychotic episode, were asked to fill in an online questionnaire. Participants ranked their priorities in treatment content, stated whether they were satisfied on these items and ranked a list of treatment goals.462 respondents ranked their treatment preferences regarding treatment content (mean age: 40.3 years; mean duration of illness: 13.5 years). Items ranked most important: "prompt assistance, preferably in own environment", "attention for medication", "appropriate attitude of the professional caregiver". More than 50% rated "unsatisfied" or "very unsatisfied" for: "practical help in resocialization", "aid to acquire autonomy" and "help with physical health". 345 participants ranked treatment goals (mean age: 40.4 years; mean duration of illness: 13.7 years). Items ranked most important: "reducing apathy and lack of initiative", "reducing disturbing or unusual experiences", "reducing confusion and concentration problems".Psychiatric services should pay great attention to early outpatient intervention with supportive counseling and an appropriate attitude of the caregiver with attention for medication use. Improvement is warranted for practical assistance, help in regaining autonomy and help with physical health.
  Pharmacopsychiatry 11/2012;
• Article: Intravenous Zolpidem Injection in a Zolpidem Abuser.

  W-Y Hsu, N-Y Chiu
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  ABSTRACT: Zolpidem abuse has been frequently observed in recent years. This study presents a case of zolpidem abuse. Although numerous cases of zolpidem dependence have been reported, this is the first case to report zolpidem intravenous injection without any history of opiate use. Clinicians should monitor patients with a history of zolpidem abuse and be aware that there is a risk of zolpidem injection.
  Pharmacopsychiatry 10/2012;
• Article: Comparing Augmentation with Non-Antidepressants over Sticking to Antidepressants after Treatment Failure in Depression: A Naturalistic Study.

  S Köhler, T Unger, S Hoffmann, B Steinacher, T Fydrich, T Bschor
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  ABSTRACT: Non-response to an antidepressant monotherapy in unipolar depression is quite common. Therefore strategies for subsequent treatment steps are necessary. However, there is a lack of direct comparisons of these different strategies. In this naturalistic study we compared the outcome to different strategies after failure of the primary antidepressant treatment.Failure of primary antidepressant monotherapy occurred in 135 patients. 98 of these patients have been administered 4 treatment strategies of the physicians' choice: lithium augmentation (Li-Augm), switching to another antidepressant (AD-Switch), combination of 2 antidepressants (AD-Comb) or augmentation with second generation antipsychotic (SGA-Augm). Primary outcome measure was the 17-item Hamilton rating scale for depression (HRSD).Patients who received Li-Augm or augmentation with SGAs showed significantly greater improvement in HRSD and BDI compared to patients with antidepressant switch or antidepressant combination. Remission rates for Li-Augm and SGA-Augm were 89.3% and 86.2% compared to 40.7% for AD-Switch and 42.9% for AD-Comb.Changing to another pharmacological class (Li-Augm or augmentation with SGAs) showed better treatment results than sticking to the class of antidepressants (AD-Switch and AD-Comb) after primary failure in response to antidepressant monotherapy in unipolar depression. The lack of randomization and absence of a non-response definition are design flaws. Controlled studies are required to confirm the findings of this trial.
  Pharmacopsychiatry 10/2012;
• Article: Serum Levels of Sodium Valproate in Patients Suffering from Bipolar Disorders: Comparing Acute and Maintenance Phases of Mania.

  G Kamalinia, S Brand, P Ghaeli, N Abedi, H Bajoghli, V Sharifi, A Zahiroddin, M Amini, M R Rouini, E Holsboer-Trachsler, A H Mohammadpoor
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  ABSTRACT: Bipolar disorders (BD) are characterized by episodes of mania and depression. There is evidence that states of psychiatric disorders impact on neurotransmitters, endocrine system and membrane transport and, therefore, it is possible that specific phases of BD differentially influence the pharmacokinetics of some drugs. The aim of the present study was to investigate the drug-disease interaction between sodium valproate, one of the major drugs used in the treatment of bipolar disorder, and acute versus maintenance states of manic episodes.37 patients (mean age±SD=37.54±11.27 years; 23 males, 14 females) suffering from bipolar disorder completed the study. Blood samples were taken during both acute and maintenance states.Neither the trough concentration (p=0.567) nor the internal clearances (p=0.729) of sodium valproate in the acute phase of mania differed statistically or descriptively from those in the maintenance phase. Marginally significant phase by gender interactions were observed.No significant effect of the acute phase of mania was observed in bipolar patients and no relationship could be found between drug pharmacokinetics and disease phase. This may be explained by specific pharmacokinetic features of the drug such as low extraction ratio values. However, phase by gender interactions indicate possible gender-related issues.
  Pharmacopsychiatry 10/2012;
• Article: Possible Association of Nicotinic Acetylcholine Receptor Gene (CHRNA4 and CHRNB2) Polymorphisms with Nicotine Dependence in Japanese Males: An Exploratory Study.

  H-I Chen, T Shinkai, K Utsunomiya, K Yamada, S Sakata, Y Fukunaka, R Hwang, V De Luca, O Ohmori, J L Kennedy, H-Y Chuang, J Nakamura
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  ABSTRACT: Smoking is a leading global cause of avoidable mortality. It has been reported that the nicotinic acetylcholine receptor (CHRNA4 and CHRNB2) genes might be associated with smoking behavior in several ethnic populations. However, no study between the 2 genes and nicotine dependence (ND) using a Japanese population has been reported.We examined the association between ND and 5 single nucleotide polymorphisms (SNPs) within the CHRNA4 and 3 SNPs within the CHRNB2 using a well characterized sample of 558 Japanese healthy male workers with a relatively homogeneous background. The Fagerström test for nicotine dependence (FTND) was used to quantify the degree of ND. Additionally, we explored the effect of gene-gene interactions of the 2 genes on ND.We found CHRNB2 rs4845652 genotypes to be associated with FTND scores under an additive genetic model: rs4845652 T-allele carriers had lower ND levels (p=0.038; when adjusted for smoking duration: p=0.052). Furthermore, we demonstrated a possible gene-gene interaction of CHRNA4 and CHRNB2 on ND in a dose-dependent manner: those smokers with CHRNA4 rs1044397 GG or GA genotypes along with CHRNB2 rs4845652 CC genotype are likely to demonstrate higher ND scores.These findings suggest that CHRNB2 rs4845652 T-allele carriers may be associated with lower levels of ND, and that certain allelic combinations of CHRNA4 and CHRNB2 might be correlated with higher ND levels. This preliminary study has certain limitations (issues such as sample size/power and multiple testing) that need to be taken into account, and the present work thus has an experimental nature.
  Pharmacopsychiatry 10/2012;
• Article: Influencing CYP Enzymes to Boost Psychiatric Treatment: A Review on Clinical Evidence.

  F M van Hasselt, Y Coehorst, B Wilffert, A J M Loonen
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  ABSTRACT: Therapeutic drug monitoring to optimize blood plasma concentrations is advised for certain psychiatric drugs. The current standard is to change the dose based on the blood plasma concentration. We present an overview that blood plasma concentrations can also be influenced by adding co-medication based on pharmacokinetic knowledge.We performed a systematic review in medical databases for pharmaco-enhancing strategies, and we present 2 cases on actively influencing CYP3A4 metabolism.4 original studies were selected on strategies to influence CYP metabolism. 2 studies on influencing CYP2D6 metabolism, 2 studies on influencing CYP1A2 metabolism. In all studies an effect of this influence was present.Ample clinical evidence is present, but shows promising results. Pharmacokinetic knowledge can and should be used in clinical settings to optimize pharmacotherapy for vulnerable patients. Also the access to expensive medication can be increased by reduction of high dosage schemes.
  Pharmacopsychiatry 10/2012;
• Article: Lithium Treatment of a Bipolar Patient with Wilson's Disease: A Case Report.

  J K Rybakowski, T Litwin, M Chlopocka-Wozniak, A Czlonkowska
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  ABSTRACT: We present the case of a male patient with a family history of both bipolar disorder (BD) and Wilson's disease (WD). Wilson's disease was diagnosed for this patient in 2008, at the age of 28 years, and shortly thereafter his bipolar illness began with depressive episodes. The patient has been treated with zinc sulphate for WD and with antidepressants for depression. In 2009, lithium was added, and in 2010 antidepressants were discontinued. During treatment with zinc sulphate, a gradual improvement of hepatic indices and a decrease of mandibulofacial dystonia was noted. In 2011, a hypomanic state occurred which subsided with an increase of the lithium dose. Since then, the patient has been mostly in a euthymic mood with subclinical hypomanic periods. We suggest that lithium may be a viable option for treating bipolar illness in patients with Wilson's disease.
  Pharmacopsychiatry 10/2012;
• Article: Changes of Serum Concentrations of Brain-Derived Neurotrophic Factor (BDNF) during Treatment with Venlafaxine and Mirtazapine: Role of Medication and Response to Treatment.

  M Deuschle, M Gilles, B Scharnholz, F Lederbogen, U E Lang, R Hellweg
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  ABSTRACT: Depression, stress and antidepressant treatment have been found to modulate the expression of brain-derived neurotrophic factor (BDNF). Recent research suggests that serum BDNF concentration is reduced in depression and that antidepressant treatment leads to an increase in serum BDNF concentration.We studied depressed patients receiving a randomized antidepressant treatment with either mirtazapine (n=29) or venlafaxine (n=27) for 28 days in a prospective design. Changes in the concentrations of serum neurotrophins in response to antidepressant treatment were assessed.There was a significant "treatment" by "medication" interaction effect on BDNF serum concentrations that indicated a decline of BDNF in venlafaxine-treated patients (7.82±3.75-7.18±5.64 ng/mL), while there was an increase in mirtazapine-treated patients (7.64±6.23-8.50±5.37 ng/mL). There was a trend for a "treatment" by "remission" interaction with a favourable clinical course being related to increasing serum BDNF.Changes in BDNF serum concentrations as a result of antidepressant therapy depend on the antidepressant and potentially on the clinical course.
  Pharmacopsychiatry 09/2012;
• Article: Aseptic Gingivitis Related to Quetiapine Hemifumarate.

  M Gahr, M A Kölle, R W Freudenmann, C Schönfeldt-Lecuona
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  ABSTRACT: Quetiapine hemifumarate (QF) is widely used in psychiatry and is associated with regularly occurring side effects such as dizziness and metabolic problems. Apart from these typical adverse events the agent has attracted attention for several rare phenomena (priapism, cholestasis, rhabdomyolysis) that indeed feature anecdotal character, but are nevertheless indispensable for a comprehensive understanding of the factual risk profile of quetiapine. We present the first report of aseptic gingivitis associated with QF in a patient with mental retardation.
  Pharmacopsychiatry 08/2012;
• Article: The Sex-Dependent Impact of Chronic Clozapine and Haloperidol Treatment on Characteristics of the Metabolic Syndrome in a Rat Model.

  M von Wilmsdorff, M-L Bouvier, U Henning, A Schmitt, T Schneider-Axmann, W Gaebel
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  ABSTRACT: An increased risk for metabolic syndrome has been described for patients with psychotic disorders. Antipsychotic drugs possibly contribute to metabolic changes.Haloperidol or clozapine was orally fed to male and female Sprague Dawley rats for 12 weeks, and body weight gain, food and water intake were measured. The serum levels of fasting glucose, HbA1c, triglycerides, cholesterol, HDL and LDL, insulin, leptin, adiponectin and ghrelin were determined. Gonadal and perirenal fat pads were removed and weighed.We found increased body weight in the male clozapine group, but decreased ones in the male haloperidol group. Clozapine-treated male and female animals had higher fasting glucose, adiponectin, leptin, ghrelin, cholesterol, HDL and LDL levels, whereas haloperidol caused increased levels of insulin and decreased values of HbA1c, cholesterol, HDL and LDL. Both antipsychotic drugs cause sex-dependent metabolic changes, which are risk factors for the metabolic syndrome, be it hyperinsulinemia under haloperidol treatment or hyperglycemia, hyperleptinemia and hyperlipidemia under clozapine.
  Pharmacopsychiatry 08/2012;