Effect of lithium carbonate on oxidative stress in patients with bipolar disorder / 上海交通大学学报（医学版）

Objective • To explore the effect on oxidative stress status of lithium treatment in bipolar disorder patients. Methods • This was a case-control study of 61 patients with bipolar disorder (8 manic patients and 53 depressed patients) matched with 49 healthy volunteers from Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine. Patients with bipolar disorder were treated with lithium carbonate for 6 weeks. The 17 Hamilton Depression Rating Scale (HAMD-17), Young Mania Rating Scale (YMRS), Clinical Global Impression-Severity of Illness (CGI-SI) were used to assess the clinical outcomes at baseline and endpoint. The serum levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured at baseline and endpoint. The oxidative stress status of the patients and controls was compared, as well as its change after lithium treatment. Results • In the patients with bipolar mania or bipolar depression, the level of SOD was lower (t=5.403, P=0.000) and the levels of GSH-Px and MDA were higher (t=8.371, P=0.000; t=6.063, P=0.000) than those of the normal population, and the level of CAT had no difference in these two groups. There was no difference in the four oxidative stress indicators between the manic state and the depressive state. There were significant differences in plasma GSH-Px and MDA contents after lithium treatment (t=4.352, P=0.000; t=2.720, P=0.009), while there was no significant difference in plasma SOD and CAT levels after lithium treatment. After treatment with lithium, MDA content in bipolar mania and bipolar depression decreased significantly (t=3.072, P=0.018; t=3.532, P=0.001), and that in the manic state decreased more. There was a significant decrease in GSH-Px level in bipolar depression (t=2.880, P=0.006). Conclusion • Oxidative stress injury exists in the patients with bipolar disorder. Lithium carbonate may adjust the imbalance of oxidative stress in these patients, and its effect in different disease states is slightly different.

Effect of mood stabilizer on gray matter volume in patients with bipolar disorder Ⅰ / 中华行为医学与脑科学杂志

Objective To investigate the abnormal change of gray matter volume in patients with euthymic bipolar disorder Ⅰ (BD-Ⅰ),and to elucidate the relationship between the use of different mood stabilizers and brain structure variations.Methods Voxel-based morphometry (VBM) was used to analyze the volume of local gray matter in 35 patients with BD-Ⅰ and 30 healthy controls(HC).The patients were divided into BD-Ⅰ with lithium group and BD-Ⅰ with valproate group according to different mood stabilizers.The volume differences of gray matter of the three groups were compared by one-way ANOVA.Results Compared with HC,BD-Ⅰ patients showed significantly reduced gray matter volume in the medial frontal cortex (MNI (x,y,z):2,34,-18),orbital frontal cortex (MNI(x,y,z):-32,22,-4),frontal operculum (MNI(x,y,z):38,18,4) and insula cortex (MNI(x,y,z):-32,22,-4) (P＜0.05).There was no significant difference in thevolume of gray matter between BD-Ⅰ with lithium group and BD-Ⅰ with valproate group(P＞0.05).Conclusion Emotional disturbance in patients with BD-Ⅰ may be associated with reduced gray matter volume in the medial frontal cortex,orbital frontal cortex,frontal operculum and insula cortex.There are not significant difference about the effects of lithium carbonate and valproate on cerebral gray matter volume in patients with BD-Ⅰ.

Psicofarmacología del suicidio II parte: Estabilizadores del ánimo y suicidio / Mood stabilizers and suicide: Part II

Lithium and anticonvulsants have been widely used as mood stabilizers (MS) in bipolar affective disorder (BAD), showing a reduction of suicide risk, even more, the anti-suicidal effect of lithium would be independent of its stabilizer property. The action mechanisms of the drug are not completely known and clinical research is hampered due to the heterogeneity of the studied samples, however, some mechanisms related to neurotransmitters metabolism and neurotrophic and neuroprotective factors have been proposed in order to explain its effect. Despite the current decline in the use of lithium as a MS it remains as the anti-suicidal drug of choice in bipolar patients.

El litio y los anticonvulsivantes han sido ampliamente empleados como estabilizadores del ánimo (EA) en el trastorno afectivo bipolar (TAB), demostrando además una reducción del riesgo de suicidio. En el caso particular del litio, dicho efecto sería independiente de su acción estabilizadora. Si bien los mecanismos de acción de la droga no son completamente conocidos y la investigación clínica se ve dificultada debido a la heterogeneidad de las muestras estudiadas, se han propuesto distintas vías que explicarían su efecto, relacionadas con el metabolismo de los neurotransmisores y con factores neurotróficos y neuroprotectores. Pese a la disminución actual en el uso del litio como EA, continúa siendo el fármaco antisuicida de elección en pacientes bipolares.

Three Mood Stabilizers for Inhibition of Ouabain-induced ERK1/2 Phosphorylation in Astrocytes / 中国医科大学学报

Objective To investigate the effets of three mood stabilizers on ouabain?induced ERK1/2 phosphorylation in astrocytes. Methods As?trocytes were treated with different agents and divided into different groups accordingly,namely,the control group with saline,the group with oua?bain,the group with mood stabilizers(lithium carbonate,carbamazepine,sodium valproate)and the group with ouabain+mood stabilizers. The phosphorylation of ERK1/2 in each group was analyzed by Western blot. Results Compared with saline and mood stabilizer groups,the phosphoryla?tion of ERK1/2 was increased in the ouabain group,with statistical significance(P<0.05). There was no significant difference in ERK1/2 phosphoryla?tion between the group with ouabain+mood stabilizers and the control or mood stabilizer group. Conclusion The three kinds of mood stabilizers can inhibit ouabain?induced ERK1/2 phosphorylation in astrocytes.

Pharmacotherapy of Bipolar Disorder with Quetiapine: A Recent Literature Review and an Update

Bipolar disorder is a chronic, recurrent condition with the usual onset during adolescence or early adulthood. In the Diagnostic and Statistical Manual of Mental Disorders 5th edition, it is conceptualized as a spectrum disorder usually associated with such comorbidities as anxiety disorders and substance use disorders. It is a relatively prevalent condition often complicated by mixed episodes, rapid cycling, subsyndromal symptoms, and treatment refractoriness. In spite of carrying substantial morbidity and mortality, effective treatments are few and far between and conventional mood stabilizers are often unsuccessful in controlling the various manifestations of the disorder. In this scenario, second generation antipsychotics are emerging as treatments with valid efficacy in all phases of bipolar disorder. Quetiapine is a versatile atypical antipsychotic which was first approved for the treatment of schizophrenia, but latter on the basis of controlled studies earned United States Food and Drug Administration's approval for acute as well as maintenance treatment of this difficult to treat condition. In this review, recently published studies in the last 10 years were examined to update the knowledge about the efficacy and safety of quetiapine in the treatment of bipolar disorder. The medication's clinical pharmacology was first considered followed by a literature review summarizing its uses in bipolar disorder. The conclusion was that quetiapine was efficacious in manic, mixed and depressive episodes and as a maintenance agent with a good tolerability profile.

Histone deacetylase activity and brain-derived neurotrophic factor (BDNF) levels in a pharmacological model of mania

Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity. .

A Trend of Drug Use in Inpatients with Bipolar Disorder: Comparing 2009-2012 with 1998-2001 in One University Hospital / 대한정신약물학회지

OBJECTIVE: The aim of this study was to monitor changes of prescription trends for bipolar disorder in inpatient settings in one university hospital. METHODS: A retrospective chart review was performed and data of 188 cases (2009-2012) and 118 cases (1998-2001) with a diagnosis of bipolar disorder were collected. Data on demographic variables, duration of hospitalization, kinds of psychotropic medications and the patterns of prescription over each four-year period were analyzed. RESULTS: The proportion of patients with manic episode was decreased, whereas those of mixed and depressive episodes were increased. The use of lithium was decreased with the increased use of valproate. Increased use of lamotrigine in depressive episode was prominent. The use of combination treatment with mood stabilizers and antipsychotics was almost same level in both periods. The use of typical antipsychotics was significantly decreased and that of atypical antipsychotics was increased. Especially, the use of quetiapine showed great increase. In bipolar depression, the use of antidepressant was increased. CONCLUSION: This study showed significant changes have occurred in the prescription patterns in patients with bipolar disorder in the last four years. These results seem to reflect the accumulating evidence-based data for the treatment of bipolar disorder, and will provide the useful information to clinicians in practical situations.

Subclinical Hypothyroidism in Patients with Bipolar Disorders Managed by Lithium or Valproic Acid

OBJECTIVES: To investigate the pattern of subclinical hypothyroidism (SCH) in patients with bipolar disorders managed by lithium or valproic acid. METHODS: The study participants were 106 patients with DSM-IV bipolar disorders receiving planned maintenance treatment at the Mood Disorders Clinic of Seoul National University Bundang Hospital (aged between 17 and 64, mean duration of follow-up = 875.65 days). Using the bipolar disorder registry, thyroid function data were analyzed to assess the frequency of and the risk factors for SCH in patients managed by lithium (n = 64) or valproic acid (n = 42) for more than 5 months. RESULTS: Overall frequencies of SCH were 20.3% (13/64) in the lithium group, 14.3% (6/42) in the valproic acid group, and between the two groups there is no difference (p = 0.43). No differences were observed in the potential risk factors for SCH between the two groups including age, sex, subtype of bipolar disorder, baseline TSH, and concomitant antipsychotic use. In cases with SCH, thyroid-stimulating hormone (TSH) showed a tendency to increase at 3 month after the initiation of lithium or valproic acid. A gradual increase in the number of patients showing SCH was found within the first 3 years of medication. CONCLUSIONS: With regular monitoring and careful assessment, there was no difference in the risk of SCH between lithium and valproic acid maintenance. The risk of mood stabilizer-associated SCH may gradually increase within 3 years following the commencement of medication, thereby mandating close monitoring for the first 3 years of treatment. Further studies with large sample size would be needed to confirm these findings.

Risperidone Combination in the Acute Treatment of Bipolar Mania and Mixed Episode: Prospective, Multicenter, Open Trial / 대한정신약물학회지

OBJECTIVE: Although mood stabilizer monotherapy is the recommended initial therapy for bipolar disorder, the use of atypical antipsychotics in bipolar patients is increasing recently. Moreover, the medical literature is demonstrating that the combination of atypical antipsychotics and mood stabilizers is a more effective therapy. The goal of this study was to assess the efficacy of risperidone in patients with acute manic and mixed state of bipolar disorder. METHODS: This study was a 4-week, open-label, combination, prospective investigation using risperidone in combination with mood stabilizers. In total, 114 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed episode, were recruited. Risperidone was given in combination with mood stabilizers in doses according to clinical response and tolerability. Efficacy was assessed with the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Depression (HAMD), the Brief Psychiatric Rating Scale (BPRS), Global Assessment Scale (GAS), and the Clinical Global Impressions Scale-Bipolar (CGI-BP). The Simpson-Angus Rating Scale (SARS) was applied to assess extrapyramidal symptoms. RESULTS: The combination of risperidone with mood stabilizers produced highly significant improvements (p<0.001) on the YMRS, HAMD, BPRS, GAS, and CGI-BP at both 1 week and 4 weekweeks. Analysis of the YMRS, BPRS, GAS, and CGI-BP scores revealed significant improvement in both the manic and mixed group. The HAMD score was decreased only in the mixed group. Body weight was increased significantly after 1 week. Risperidone was well tolerated, and adverse events were mostly mild, with the most frequent extrapyramidal symptoms and sedation. CONCLUSION: Our findings suggest that the combination of risperidone with mood stabilizers was an effective and safe treatment for acute manic symptoms and coexisting depressive symptoms of bipolar disorder. Randomized, double-blind, placebo or active controlled studies are needed.

Recent 5-Year Trends of Prescription Patterns in Inpatients with Bipolar Disorder in Four Hospitals / 대한정신약물학회지

OBJECTIVE: The aim of this study was to monitor changes of prescription patterns for bipolar disorder in clinical settings during the last five years in four psychiatric treatment centers. METHODS: A retrospective chart review of data of 601 patients with bipolar disorder was performed between January 2001 and December 2005 from four psychiatric centers in Seoul and GyeongGi-Do. Data on demograpnic variables, clinical characteristics, and the types and dosages of mood stabilizers and antipsychotics, and the patterns of prescriptions over the five-year period were analyzed. RESULTS: The use of valproate has increased, whereas the percentage of lithium use has decreased. The combined prescription of valproate and lithium remained constant at 12% over the five-year period. The prescription of newer-class of mood stabilizers such as lamotrigine and topiramate was few. Most of the patients in our study were on more than two psychotropic agents, with the most common discharge medication being a combination of a mood stabilizer and an antipsychotic (81.9%). The use of atypical antipsychotics has increased its share from 71.4% in 2001 to 92.3% in 2005. Among the atypical antipsychotics, Quetiapine use showed the most rapid increase since year 2001 and ranked as the most frequenctly used antipsychotics for bipolar disorder in 2005 (38.5% of antipsychotics). Especially, in those without psychotic features, quetiapine was the most frequently used antipsychotics (51.2% in 2005). In those with psychotic features, risperidone (39.1%) was more frequently used than quetiapine (28.3%). CONCLUSION: The present study showed that significant changes have occurred in the prescription patterns of mood stabilizers and antipsychotics and the rate of combination therapy for patients with bipolar disorder in the last five years. These results seem to reflect the introduction of new agents and the accumulating evidencebased data for the treatment of bipolar disorder, and will provide the useful information to clinicians for the establishment of better treatment guidelines for patients with bipolar disorder.

Polypharmacy in Schizophrenic Inpatients: The Comparison between 1997 and 2003 in One University Hospital / 대한정신약물학회지

OBJECTIVE: Up to recently, the standard pharmacotherapy of schizophrenia has been monotherapy, use of one antipsychotic medication. However, polypharmacy in patients with schizophrenia is a common practice with little basis in well-controlled studies. In this study, we explored the patterns of pharmacotherapy in inpatient with schizophrenia by comparing prescribed medications at discharge between the year 1997 and the year 2003. METHODS: The medical records of patients who discharged with the diagnosis of schizophrenia from department of psychiatry, St. Mary's hospital in 1997 and 2003 were reviewed. The psychotropic medications at discharge were compared. The length of stay at the hospital and the incidence of adverse drug reactions were also compared. For statistics, chi-square test and independent t-test were performed. RESULTS: Data of 96 patients who discharged in 1997 and 2003 were analyzed. Patients prescribed with more than two kinds of antipsychotics were 7 of 96 in 1997 (7.2%) and 12 of 72 (16.7%), but the difference is not statistically significant (p=0.058). Patients prescribed with antipsychotics and mood stabilizers were 9 (9.3%) in 1997 and 18 (25%) in 2003. The difference is statistically significant (p=0.010). Especially, carbamazepine occupied most part of mood stabilizer use (89%) in 1997 but valproate use was increased much in 2003 (56%). Patients who were administered with anxiolytics (p=0.001) or anti-Parkinson agents (p<0.001) were decreased in 2003 compared with 1997. There were no statistically significant differences in the incidence of adverse drug reactions and the length of stay at the hospital. CONCLUSION: This study found that hospitalized patients with schizophrenia are being treated with more psychotropic medications, including more than 1 antipsychotic.

Feasibility of Korean Medication Algorithm for Bipolar Disorder(II): Choice of Medications / 대한정신약물학회지

OBJECTIVE: The Korean College of Neuropsychopharmacology and the Korean Academy of Schizophrenia developed the Korean algorithm project for bipolar disorder to aid clinical decisions. The purpose of this study was to investigate the prescribing tendency of psychopharmacological agents such as mood stabilizers and antipsychotics according to the Korean Medication Algorithm for Bipolar Disorder (KMAP-BP) in clinical settings. METHODS: Ninety-two patients were treated according to the algorithm. Among them the selection and dose of drugs were investigated in 71 patients whose precise medication records were available. RESULTS: Lithium (n=37) and divalproex (n=33) were used as mood stabilizers and combination treatment with both medications was done for one patient. Carbamazepine was not used. During the maintenance period, dosage of mood stabilizer was higher for mixed and psychotic mania compared with euphoric mania. Antipsychotic drug was co-administrated with a mood stabilizer from the beginning of the treatment in 62 of 71 patients and risperidone (69.4%) was the most preferred drug. Of those 62 patients who were treated with antipsychotics, 24 patients were initially taking anti-parkinsonian agents. CONCLUSION: This study investigated the prescribing tendency of clinicians who practiced according to the KMAP-BP. Considering the results of this study, further research is needed to revise KMAP-BP.

A Trend of Drug Use in Inpatients with Bipolar Disorder: A 4-Year Naturalistic Study in One Hospital / 대한정신약물학회지

OBJECTIVE: As the limitation of lithium that is representative of the treatment in bipolar disorder is known, the use of other mood stabilizers such as carbamazepine, valproate have been increased. And with the development of pharmacotherapy, combinations of atypical antipsychotics and other drugs are a general tendency in the treatment of bipolar disorder. This study was to investigate the prescription trends in psychiatric inpatients with bipolar disorder at a university hospital and to put knowledge to practical use. METHODS: Data of 118 cases with a diagnosis of bipolar disorder according to DSM-IV from January 1998 to December 2001 were collected. Data on demographic data, duration of hospitalization, and kinds and dosages of mood stabilizers and antipsychotics were analyzed. RESULTS: In 118 subjects, 52 were male and 66 were female. In term of diagnosis, subjects with bipolar I disorder were 116 (98.3%) and subjects with bipolar II disorder were 2 (1.7%). And subjects with manic episode were 96 (81.4%), subjects with depressive episode were 17 (14.4%), subjects with hypomanic episode were 3 (2.5%) and subjects with mixed episode were 2 (1.7%). From 1998 to 2001, 95.8% of total cases were treated with the combination therapy of mood stabilizers and antipsychotics, and only 4.2% were treated with the monotherapy of a mood stabilizer. Considering mood stabilizers, the use of single mood stabilizer was 54.2% and two or more mood stabilizers combination was 45.8%. Lithium was the most commonly used mood stabilizer, and the combination of lithium and carbamazepine was the second. The mean dosage was 1060+/-207 mg/day for lithium, 665+/-131 mg/day for carbamazepine, 1056+/-258 mg/day for valproate. There was no significant change in terms of dosages used in every year. Comparing year 1998 to year 2001, the combination of mood stabilizers and antipsychotics has been increased from 90.3% to 100%. The ratio of using two or more antipsychotics decreased from 38.7% to 10.3%, but the ratio of single antipsychotics use increased from 54.8% to 89.7%. Considering the ratio of antipsychotics, typical antipsychotics decreased from 38.7% to 6.9%, but atypical antipsychotics increased from 61.3% to 93%. CONCLUSION: With the rapid and dramatic progress of psychopharmacology, the prescription trend of the pharmacotherapy in the bipolar disorder has been changed. This study suggest that the use of atypical antipsychotics has increased profoundly. We think it reflects the current progress of the treatment in the bipolar disorder.

A Trend of Drug Use in Inpatients with Bipolar Disorder: A 4-Year Naturalistic Study in One Hospital / 대한정신약물학회지

OBJECTIVE: As the limitation of lithium that is representative of the treatment in bipolar disorder is known, the use of other mood stabilizers such as carbamazepine, valproate have been increased. And with the development of pharmacotherapy, combinations of atypical antipsychotics and other drugs are a general tendency in the treatment of bipolar disorder. This study was to investigate the prescription trends in psychiatric inpatients with bipolar disorder at a university hospital and to put knowledge to practical use. METHODS: Data of 118 cases with a diagnosis of bipolar disorder according to DSM-IV from January 1998 to December 2001 were collected. Data on demographic data, duration of hospitalization, and kinds and dosages of mood stabilizers and antipsychotics were analyzed. RESULTS: In 118 subjects, 52 were male and 66 were female. In term of diagnosis, subjects with bipolar I disorder were 116 (98.3%) and subjects with bipolar II disorder were 2 (1.7%). And subjects with manic episode were 96 (81.4%), subjects with depressive episode were 17 (14.4%), subjects with hypomanic episode were 3 (2.5%) and subjects with mixed episode were 2 (1.7%). From 1998 to 2001, 95.8% of total cases were treated with the combination therapy of mood stabilizers and antipsychotics, and only 4.2% were treated with the monotherapy of a mood stabilizer. Considering mood stabilizers, the use of single mood stabilizer was 54.2% and two or more mood stabilizers combination was 45.8%. Lithium was the most commonly used mood stabilizer, and the combination of lithium and carbamazepine was the second. The mean dosage was 1060+/-207 mg/day for lithium, 665+/-131 mg/day for carbamazepine, 1056+/-258 mg/day for valproate. There was no significant change in terms of dosages used in every year. Comparing year 1998 to year 2001, the combination of mood stabilizers and antipsychotics has been increased from 90.3% to 100%. The ratio of using two or more antipsychotics decreased from 38.7% to 10.3%, but the ratio of single antipsychotics use increased from 54.8% to 89.7%. Considering the ratio of antipsychotics, typical antipsychotics decreased from 38.7% to 6.9%, but atypical antipsychotics increased from 61.3% to 93%. CONCLUSION: With the rapid and dramatic progress of psychopharmacology, the prescription trend of the pharmacotherapy in the bipolar disorder has been changed. This study suggest that the use of atypical antipsychotics has increased profoundly. We think it reflects the current progress of the treatment in the bipolar disorder.

Trends in Pharmacotherapy of the Hospitalized Patients with Bipolar Disorder: A Twele-year Naturalistic Study / 대한정신약물학회지

OBJECTIVE: The purpose of this study was to examine the pharmacological treatment patterns in inpatients with bipolar disorder at a university hospital, and to establish appropriate clinical practice guideline in light of recent advances of pharmacotherapy of bipolar disorder. METHODS: A total of 454 first-admission cases with a diagnosis of bipolar disorder or schizoaffective disorder from 1990 to 2001 were analyzed with regard to the clinical characteristics and the use of mood stabilizers, antidepressants and antipsychotics. RESULTS: In manic, hypomanic, and mixed episodes, there has been a substantial increase in the use of valproate while the use of lithium has decreased. Antipsychotic drugs were prescribed as combination regimen in over 80% of total cases. In 44.6% of bipolar depression cases, mood stabilizers were not prescribed. In 70.7% of bipolar depression cases not receiving mood stabilizers, antidepressant monotherapy was utilized. The use of SSRIs and RIMA has increased, while a decrease was observed for TCA. There has been a tendency of the increased use of atypical antipsychotics. In particular, clozapine monotherapy has increased in mood stabilizer resistant cases. CONCLUSIONS: The results of the present study suggest that the prescription patterns have changed in general agreement with recent advances of pharmacotherapy of bipolar disorder during the past twelve years. However, there was clear tendency to use antipsychotics rather than other mood stabilizers as the combination regimen. Moreover, accurate diagnosis and careful reconsideration for pharmacological treatment strategies are required in bipolar depression, mixed states, and rapid cycling.

Drug-Drug Interactions: Mood Stabilizers and Anti-Anxiety Drugs

Pharmacotherapy of bipolar disorder is a rapidly evolving field. Mood stabilizers and anticonvulsants have varying biochemical profiles which may predispose them to different adverse effects and drug-drug interactions. Several of the new anticonvulsants appear less likely to have the problems with drug-drug interaction. To provide more effective combination pharmacotherapies, clinicians should be allowed to anticipate and avoid pharmacokinetic and pharmacodynamic drug-drug interactions. We reviewed the role of cytochrome P450 isozymes in the metabolism of the drugs and their interactions. The drug-drug interactions of several classes of drugs which used as mood stabilizers and new anticonvulsants, some of which may have psychotropic profiles, are discussed mainly in this article. Finally, potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs are discussed briefly.