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2.
Indian J Psychol Med ; 42(1): 87-92, 2020.
Article in English | MEDLINE | ID: mdl-31997870

ABSTRACT

BACKGROUND: There is a paucity of data related to anxiety levels in patients undergoing day care surgery in India. METHODS: Preoperative anxiety was assessed using Amsterdam Preoperative Anxiety and Information Scale (APAIS) 1 day before surgery and on the day of surgery, and the patients were categorized as cases (APAIS score ≥13) and controls (APAIS score <13). Sociodemographic characteristics, clinical features, and fears associated with anesthesia and surgery were also noted. RESULTS: Out of the 399 patients recruited, 58.1% experienced significant preoperative anxiety. The fear of needles (P = 0.002), fear of waking up during the surgery (P < 0.001), and the patient's need of additional information regarding anesthesia and surgery (P < 0.001) were significantly associated with preoperative anxiety. CONCLUSION: A significant proportion of patients scheduled for day care surgery have preoperative anxiety. A preanesthetic workup of a patient with adequate clarification about their doubts and fears related to anesthesia and surgery is recommended to bring down the level of anxiety.

3.
J Clin Psychopharmacol ; 39(6): 644-648, 2019.
Article in English | MEDLINE | ID: mdl-31688448

ABSTRACT

PURPOSE/BACKGROUND: Clozapine clearance is influenced by sex, smoking status, ethnicity, coprescription of inducers or inhibitors, obesity, and inflammation. In 126 Beijing inpatients, we measured repeated trough steady-state serum concentrations and identified 4% (5/126) who were phenotypical poor metabolizers (PMs); none were ultrarapid metabolizers (UMs). They were defined as being 2 SDs beyond the means of total clozapine concentration/dose ratios stratified by sex and smoking. Using this definition, this study explores the prevalence of PMs and UMs using data from 4 already published Asian samples. Three samples were East Asian (Beijing 2, Taipei, and Seoul); one was from South India (Vellore). FINDINGS/RESULTS: The prevalence of phenotypical PMs ranged from 2% to 13%, but inflammation was not excluded. The prevalence was 7% (14/191) for Beijing 2, 11% (8/70) for Taipei, 13% (9/67) for Seoul, and 2% (2/101) for the Vellore sample. Five phenotypic PMs appeared to be associated with extreme obesity. Phenotypic UM prevalence ranged from 0% to 1.6% but may be partly explained by lack of adherence. A Vellore phenotypic UM appeared to be associated with induction through high coffee intake. IMPLICATIONS/CONCLUSIONS: Approximately 10% of Asians may be clozapine PMs and may need only 50 to 150 mg/d to get therapeutic concentrations. Future studies combining gene sequencing for new alleles with repeated concentrations and careful control of confounders including inhibitors, inflammation, and obesity should provide better estimations of the prevalence of phenotypic clozapine PMs across races. Clozapine UM studies require excluding potent inducers, careful supervision of compliance in inpatient settings, and multiple serum concentrations.


Subject(s)
Antipsychotic Agents/metabolism , Asian People/ethnology , Clozapine/metabolism , Coffee/metabolism , Inflammation/metabolism , Obesity/metabolism , Adult , Beijing/ethnology , Female , Humans , India/ethnology , Male , Prevalence , Republic of Korea/ethnology , Taiwan/ethnology
4.
Asian J Psychiatr ; 34: 47-53, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29635223

ABSTRACT

BACKGROUND: Cognitive deficits, self-reported or found following electroconvulsive therapy (ECT), and their correlates are diverse. Despite the characteristics of people receiving ECT in Asia differ widely from the west, pertinent research from Asia remains sparse. METHODS: We investigated the correlates of self-reported, mini-mental status examination (MMSE) defined, and autobiographical memory deficits in a cohort that received ECT in a south Indian tertiary-care setting. 76 consecutive consenting people were recruited within seven days of completing their ECT course. Memory was assessed by a subjective Likert scale, MMSE, and an autobiographical memory scale (AMS). Psychopathology was assessed by brief psychiatric rating scale, and serum cortisol levels were estimated by chemi-luminescence immunoassays. Relevant sociodemographic and clinical data were collected from the participants, and their medical records. The correlates were analysed using generalised linear models after adjusting for the effects of potential confounders. RESULTS: Self-reported, MMSE-defined, and autobiographical memory deficits were present in 27.6% (95%CI 17.6-37.7%), 42.1% (95%CI 31.0-53.2%), and 36.8% (95%CI 26.0-47.7%) of participants, respectively. Agreement between the memory deficits was poor. Age, less education, duration of illness, hypothyroidism, and past history of another ECT course were significantly associated with MMSE-defined deficits. Age, anaemia, past ECT course, and pre-ECT blood pressure were significantly associated with autobiographical memory deficits, while residual psychopathology and cortisol levels were significantly associated with self-reported memory deficits. CONCLUSION: Self-reported, MMSE-defined, and autobiographical memory deficits are common at the completion of ECT course, and their correlates differ. All service users receiving ECT need periodic cognitive assessments evaluating multiple cognitive domains.


Subject(s)
Electroconvulsive Therapy/adverse effects , Hydrocortisone/blood , Memory Disorders/etiology , Memory Disorders/physiopathology , Memory, Episodic , Schizophrenia/therapy , Adult , Case-Control Studies , Female , Humans , India , Male , Memory Disorders/diagnosis , Mental Status and Dementia Tests , Schizophrenia/blood , Self Report , Young Adult
5.
J Neurosurg Spine ; 28(1): 23-32, 2018 01.
Article in English | MEDLINE | ID: mdl-29125433

ABSTRACT

OBJECTIVE Although various predictors of postoperative outcome have been previously identified in patients with Chiari malformation Type I (CMI) with syringomyelia, there is no known algorithm for predicting a multifactorial outcome measure in this widely studied disorder. Using one of the largest preoperative variable arrays used so far in CMI research, the authors attempted to generate a formula for predicting postoperative outcome. METHODS Data from the clinical records of 82 symptomatic adult patients with CMI and altered hindbrain CSF flow who were managed with foramen magnum decompression, C-1 laminectomy, and duraplasty over an 8-year period were collected and analyzed. Various preoperative clinical and radiological variables in the 57 patients who formed the study cohort were assessed in a bivariate analysis to determine their ability to predict clinical outcome (as measured on the Chicago Chiari Outcome Scale [CCOS]) and the resolution of syrinx at the last follow-up. The variables that were significant in the bivariate analysis were further analyzed in a multiple linear regression analysis. Different regression models were tested, and the model with the best prediction of CCOS was identified and internally validated in a subcohort of 25 patients. RESULTS There was no correlation between CCOS score and syrinx resolution (p = 0.24) at a mean ± SD follow-up of 40.29 ± 10.36 months. Multiple linear regression analysis revealed that the presence of gait instability, obex position, and the M-line-fourth ventricle vertex (FVV) distance correlated with CCOS score, while the presence of motor deficits was associated with poor syrinx resolution (p ≤ 0.05). The algorithm generated from the regression model demonstrated good diagnostic accuracy (area under curve 0.81), with a score of more than 128 points demonstrating 100% specificity for clinical improvement (CCOS score of 11 or greater). The model had excellent reliability (κ = 0.85) and was validated with fair accuracy in the validation cohort (area under the curve 0.75). CONCLUSIONS The presence of gait imbalance and motor deficits independently predict worse clinical and radiological outcomes, respectively, after decompressive surgery for CMI with altered hindbrain CSF flow. Caudal displacement of the obex and a shorter M-line-FVV distance correlated with good CCOS scores, indicating that patients with a greater degree of hindbrain pathology respond better to surgery. The proposed points-based algorithm has good predictive value for postoperative multifactorial outcome in these patients.


Subject(s)
Algorithms , Arnold-Chiari Malformation/diagnosis , Arnold-Chiari Malformation/surgery , Syringomyelia/diagnosis , Syringomyelia/surgery , Adult , Aged , Arnold-Chiari Malformation/physiopathology , Cohort Studies , Female , Gait , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Motor Activity , Postural Balance , Predictive Value of Tests , Prognosis , Syringomyelia/physiopathology , Treatment Outcome , Young Adult
6.
Pharmacogenet Genomics ; 28(1): 31-35, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29087970

ABSTRACT

Clozapine is the drug of choice for treatment-resistant schizophrenia. However, its use is associated with variable clinical responses and serious adverse effects. Polymorphisms in genes encoding proteins involved in synaptic neurotransmission may account for such variability. Here, we studied independent and epistatic genetic associations of polymorphisms in DRD4 (120-bp duplication) and COMT (Val158Met) with clinical response to clozapine in people with treatment-resistant schizophrenia. We studied 93 participants who were on stable doses of clozapine for at least 12 weeks. A total score of less than or equal to 35 on the Brief Psychiatric Rating Scale was defined as a clinical response. The genetic associations were tested using logistic regression analyses. Neither polymorphism studied was found to be independently associated with response to clozapine. However, a statistically significant gene-gene interaction was observed between the polymorphisms. Participants with the COMT Val/Met or Met/Met genotype, who also had one or two DRD4 120-bp alleles (120/240 and 120/120), showed significantly better clinical response to clozapine. Our results highlight the importance of investigating gene-gene interactions, while studying the pharmacogenetics of clozapine.


Subject(s)
Catechol O-Methyltransferase/genetics , Clozapine/administration & dosage , Drug Resistance , Receptors, Dopamine D4/genetics , Schizophrenia/drug therapy , Adult , Amino Acid Substitution , Chromosome Duplication , Clozapine/pharmacology , Drug Resistance/drug effects , Epistasis, Genetic , Female , Humans , Male , Middle Aged , Pharmacogenomic Variants , Schizophrenia/genetics , Treatment Outcome
7.
Curr Opin Psychiatry ; 30(5): 334-338, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28704238

ABSTRACT

PURPOSE OF REVIEW: Patient and physician perspectives about mental health, illness, and recovery, which affect different aspects of help seeking and healthcare, needs to be understood and theorized. RECENT FINDINGS: People seem to simultaneously hold multiple and contradictory illness beliefs and seek help from diverse sources of cure and healing. Explanatory models elicited at baseline do not predict outcomes of illness, change over time, and are dependent on the interaction between the trajectory of individual's illness and the sociocultural milieu. Illness narratives contextualize the patient, describe the patient's reality and his/her ways of coping, and attempt to make sense of illness experiences, control them, and improve quality of life. On the other hand, diversity of beliefs among psychiatrists, family physicians, and public health specialists is dependent on their disciplinary perspectives. Nevertheless, the variability within psychiatric syndromes and the inability to predict individual trajectories of illness support cultural beliefs about uncertainties of life. These are identified by cultures through idioms and metaphors and labeled as luck, chance, karma, fate, punishment by God, evil spirits, black magic, disease and so on. SUMMARY: There is a need for a broad-based approach to mental health, which allows individuals to make sense of their contexts and find meaning in life.


Subject(s)
Attitude of Health Personnel , Health Knowledge, Attitudes, Practice , Mental Disorders/psychology , Mental Health , Recovery of Function/physiology , Adaptation, Psychological/physiology , Humans , Quality of Life/psychology
8.
Arab J Urol ; 14(4): 269-274, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27900216

ABSTRACT

OBJECTIVES: To identify factors predicting renal recovery in patients presenting with renal failure secondary to bilateral obstructing urolithiasis. PATIENTS AND METHODS: Data from electronic records of consecutive adult patients presenting with bilateral obstructing urolithiasis between January 2007 and April 2011 were retrieved. Ultrasonography of the abdomen, and kidney, ureter, bladder (KUB study) X-ray or abdominal non-contrast computed tomography confirmed the diagnosis. Interventional radiologists placed bilateral nephrostomies. Definitive intervention was planned after reaching nadir creatinine. Renal recovery was defined as nadir creatinine of ⩽2 mg/dL. RESULTS: In all, 53 patients were assessed, 50 (94.3%) were male, and 18 (33.9%) were aged ⩽40 years. Renal recovery was achieved in 20 patients (37.7%). A symptom duration of ⩽25 days (P < 0.01), absence of hypertension (P = 0.018), maximum renal parenchymal thickness of >16.5 mm (P = 0.001), and haemoglobin >9.85 g/dL (P < 0.01) were significant on unadjusted analysis. Symptom duration of ⩽25 days alone remained significant after adjusted analysis. Symptom duration of ⩽25 days (hazard ratio (HR) 13.83, 95% confidence interval (CI) 4.52-42.26; P < 0.01), parenchymal thickness of ⩾16.5 mm (HR 5.91, 95% CI 1.94-17.99; P = 0.002), and absence of hypertension (HR 9.99, CI 95% 1.32-75.37; P = 0.026) were significantly related to time to nadir creatinine. Symptom duration of ⩽25 days (HR 17.44, 95% CI 2.48-122.79; P = 0.004) alone remained significant after adjusted analysis. A symptom duration of ⩽25 days (P = 0.007) was 22-times more likely to indicate renal recovery. CONCLUSIONS: Shorter symptom duration (⩽25 days) is predictive of renal recovery in renal failure secondary to bilateral obstructive urolithiasis.

9.
Am J Geriatr Psychiatry ; 24(12): 1196-1208, 2016 12.
Article in English | MEDLINE | ID: mdl-27743841

ABSTRACT

OBJECTIVE: Although depression among older people is an important public health problem worldwide, systematic studies evaluating its prevalence and determinants in low and middle income countries (LMICs) are sparse. The biopsychosocial model of depression and prevailing socioeconomic hardships for older people in LMICs have provided the impetus to determine the prevalence of geriatric depression; to study its associations with health, social, and economic variables; and to investigate socioeconomic inequalities in depression prevalence in LMICs. METHODS: The authors accessed the World Health Organization Study on Global AGEing and Adult Health Wave 1 data that studied nationally representative samples from six large LMICs (N = 14,877). A computerized algorithm derived depression diagnoses. The authors assessed hypothesized associations using survey multivariate logistic regression models for each LMIC and pooled their risk estimates by meta-analyses and investigated related socioeconomic inequalities using concentration indices. RESULTS: Cross-national prevalence of geriatric depression was 4.7% (95% CI: 1.9%-11.9%). Female gender, illiteracy, poverty, indebtedness, past informal-sector occupation, bereavement, angina, and stroke had significant positive associations, whereas pension support and health insurance showed significant negative associations with geriatric depression. Pro-poor inequality of geriatric depression were documented in five LMICs. CONCLUSIONS: Socioeconomic factors and related inequalities may predispose, precipitate, or perpetuate depression amongolder people in LMICs. Relative absence of health safety net places socioeconomically disadvantaged older people in LMICs at risk. The need for population-based public health interventions and policies to prevent and to manage geriatric depression effectively in LMICs cannot be overemphasized.


Subject(s)
Depression/etiology , Developing Countries/statistics & numerical data , Health Status , Socioeconomic Factors , Aged , Aging/psychology , Depression/epidemiology , Educational Status , Female , Global Health/statistics & numerical data , Health Status Disparities , Humans , Literacy/psychology , Literacy/statistics & numerical data , Logistic Models , Male , Poverty/psychology , Poverty/statistics & numerical data , Prevalence , Sex Factors , World Health Organization
10.
Psychiatr Genet ; 24(6): 273-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25304228

ABSTRACT

The use of clozapine, an effective antipsychotic drug used in treatment-resistant schizophrenia, is associated with adverse effects. Sialorrhea is one such effect, which can be distressing for many patients. Studies on the pharmacogenetics of the adverse effects of clozapine are limited. The aim of the present study was to determine whether clozapine-induced sialorrhea is associated with a 120 base-pairs (bp) tandem duplication polymorphism in the dopamine receptor subtype D4 (DRD4) gene. Ninety-five patients, mean age 35.43±9.43 years, with treatment-resistant schizophrenia and on clozapine were included in the study. Development of sialorrhea in response to the drug, as manifested by drooling of saliva, was documented in 45 (47.4%) patients. Genotyping of the patients was carried out to detect the presence of the polymorphism of interest. Clozapine-induced sialorrhea was found to be associated significantly with the 120-bp duplication in DRD4. The association was found to fit a log-additive model with an odds ratio of 2.95 (95% confidence interval 1.51-5.75; P=0.0006). Thus, the presence of the 120-bp duplication in DRD4 appears to confer a risk for sialorrhea in response to clozapine therapy. The underlying pathophysiology and clinical significance of this phenomenon warrant further investigation.


Subject(s)
Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Polymorphism, Genetic , Promoter Regions, Genetic , Receptors, Dopamine D4/genetics , Sialorrhea/chemically induced , Adult , Female , Humans , Male , Middle Aged , Sialorrhea/genetics
11.
Australas Psychiatry ; 22(5): 458-60, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25008096

ABSTRACT

OBJECTIVE: To assess the prevalence of personality disorders in general medical geriatric admissions. METHODS: Forty of 508 general medical geriatric admissions screened at a large tertiary hospital, who were eligible as defined by a Mini-Mental State Examination score of over 23 and capable of informed consent, were assessed by direct interview and discussion with the patient's family or close contact to determine personality traits. RESULTS: Eight (20%) of these patients were found to satisfy DSM-IV criteria for a personality disorder. They were found to have significantly lower global assessments of functioning, impaired overall functioning and lower quality of life compared with non-personality disordered patients. None of their personality disorders had been recognised by their treating teams. CONCLUSIONS: This study supports the need for systematic research into the area and the need for increased clinical awareness of the issues.


Subject(s)
Personality Disorders/epidemiology , Aged , Aged, 80 and over , Female , Geriatric Assessment/statistics & numerical data , Humans , Inpatients/statistics & numerical data , Male , New South Wales/epidemiology , Personality Disorders/diagnosis , Prevalence , Tertiary Care Centers/statistics & numerical data
12.
J Neurosurg Spine ; 21(4): 538-46, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25014501

ABSTRACT

OBJECT: T2-weighted intramedullary increased signal intensity (ISI) on MRI in patients with cervical spondylotic myelopathy (CSM) appears to represent a wide spectrum of pathological changes that determine reversibility of cord damage. Although sharp T2-weighted ISI on preoperative imaging may correlate with poorer surgical outcomes, there are limited data on how these changes progress following surgery. In this study, the authors characterized pre-and postoperative ISI changes in patients undergoing surgery for CSM and studied their postoperative evolution in an attempt to quantify their clinical significance. METHODS: The preoperative and postoperative MR images obtained in 56 patients who underwent oblique cervical corpectomy for CSM were reviewed, and the ISI was classified into 4 subtypes based on margins and intensity: Type 0 (none), Type 1 ("fuzzy"), Type 2 ("sharp"), and Type 3 ("mixed"). The locations of the ISI were further classified as focal if they represented single discrete lesions, multifocal if there were multiple lesions with intervening normal cord, and multisegmental if the lesions were continuous over more than 1 segment. The maximum craniocaudal length of the ISI was measured on each midsagittal MR image. The Nurick grade and Japanese Orthopaedic Association (JOA) score were used to assess clinical status. The mean duration of follow-up was 28 months. RESULTS: T2-weighted ISI changes were noted preoperatively in 54 patients (96%). Most preoperative ISI changes were Type 1 (41%) or Type 3 (34%), with a significant trend toward Type 2 (71%) changes at follow-up. Multi-segmental and Type 3 lesions tended to regress significantly after surgery (p = 0.000), reducing to Type 2 changes at follow-up. Clinical outcomes did not correlate with ISI subtype; however, there was a statistically significant trend toward improvement in postoperative Nurick Grade in patients with a > 50% regression in ISI size. In addition, patients with more than 18 months of follow-up showed significant regression in ISI size compared with patients imaged earlier. On logistic regression analysis, preoperative Nurick grade and duration of follow-up were the only significant predictors of postoperative improvement in functional status (OR 4.136, p = 0.003, 95% CI 1.623-10.539 and OR 6.402, p = 0.033, 95% CI 1.165-35.176, respectively). CONCLUSIONS: There is a distinct group of patients with multisegmental Type 3 intramedullary changes who show remarkable radiological regression after surgery but demonstrate a residual sharp focal ISI at follow-up. A regression of the ISI by > 50% predicts better functional outcomes. Patients with a good preoperative functional status remain the most likely to show improvement, and the improvement continues to occur even at remote follow-up. The clinical relevance of the quality of the T2-weighted ISI changes in patients with CSM remains uncertain; however, postoperative regression of the ISI change is possibly a more important correlate of patient outcome than the quality of the ISI change alone.


Subject(s)
Cervical Vertebrae/surgery , Decompression, Surgical , Magnetic Resonance Imaging/methods , Spondylosis/pathology , Spondylosis/surgery , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Spinal Cord Compression/pathology , Spinal Cord Compression/surgery , Treatment Outcome
13.
Indian J Psychol Med ; 36(2): 179-81, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24860221

ABSTRACT

OBJECTIVES: This study attempted to follow up a cohort of women who presented to a tertiary hospital to investigate the effect of domestic violence on maternal and neonatal outcomes. MATERIALS AND METHODS: Women, between 26-34 weeks of gestation, attending the obstetrics outpatient department, were recruited and followed up until delivery. They were assessed at recruitment and after delivery using the Edinburgh Postnatal Depression Scale, the Abuse Assessment Screen, and a pro forma to assess socio-demographic and clinical characteristics. Bivariate and multivariate statistics were employed to assess statistical significance. RESULTS: One hundred and fifty women were recruited, 132 delivered in the hospital and were followed up. Domestic violence was associated with antenatal and postnatal depression, spouse's insistence of a boy baby, medical complications during pregnancy, preterm delivery, and lower birth-weight. CONCLUSION: Domestic violence has a significant impact on maternal and neonatal outcomes. Screening for domestic violence and interventions should be part of all antenatal programs. India should also employ public health approaches to change its patriarchal culture.

14.
Int J Soc Psychiatry ; 60(6): 566-74, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24097842

ABSTRACT

BACKGROUND AND AIMS: There is a dearth of data on the predictors of insight in schizophrenia. This study attempted to assess the predictors of insight in a cohort of first-episode schizophrenia followed up over 5 years. METHODS: Patients diagnosed to have Diagnostic and statistical manual of mental disorders (4th ed.; DSM-IV) schizophrenia (n = 131) were assessed prospectively for insight, psychopathology and explanatory models of illness over a 5-year period using standard instruments. Multiple linear regression and generalized estimating equations (GEE) were employed to assess predictors of insight. RESULTS: We could follow up 95 (72.5%) patients, 5 years after recruitment. A total of 65 of these patients interviewed at 60 months (68.4%) achieved remission. Cross-sectional evaluations suggest a relationship between insight, psychosis rating and explanatory models of illness with good insight and medical models associated with good outcome. However, baseline and early illness data do not predict insight scores at 5 years. Serial longitudinal assessment of insight is negatively associated with Brief Psychiatric Rating Scale (BPRS) scores and positively associated with the number of nonmedical explanatory models of illness held by patients. CONCLUSION: These findings argue that insight and explanatory models of illness are secondary to psychopathology, course and outcome. They are dependent on the trajectory of the person's illness, are not independent of the condition and call for multifaceted understanding of the issues.


Subject(s)
Comprehension , Schizophrenic Psychology , Adult , Cross-Sectional Studies , Female , Humans , India , Interview, Psychological , Male , Psychiatric Status Rating Scales , Schizophrenia/diagnosis , Self Concept
15.
Int Clin Psychopharmacol ; 28(1): 50-6, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23104241

ABSTRACT

Fixed oral doses of clozapine produce up to 45-fold interindividual variability among its serum levels in patients with treatment-resistant schizophrenia. Although the relationship between serum clozapine level and its therapeutic response is uncertain, the presence of a therapeutic window and level-dependent adverse effects require the estimation of serum clozapine levels. As routine therapeutic drug monitoring of clozapine is not feasible in many clinical settings, identification of clinical predictors of serum clozapine levels is desirable. Hence, we aimed to evaluate the clinical variables associated with serum clozapine levels. We assessed the sociodemographic and clinical profiles, cognition, disability and psychopathology of 101 consecutive patients with treatment-resistant schizophrenia on a stable dose of clozapine, using standard assessment schedules. We determined their serum clozapine levels using high-performance liquid chromatography with ultraviolet detection. While employing multivariate robust regression models, oral clozapine dose (P<0.001), caffeine intake (P=0.04) and Valproate comedication (P=0.005) were associated with serum clozapine levels. Serum clozapine levels above 750 ng/ml increased the risk of seizures (odds ratio 5.15; P=0.03). Clinical variables are useful to model a dosing nomogram for serum clozapine levels. The importance of caffeine consumption and Valproate comedication should be considered during clozapine dose adjustments to enhance its therapeutic response and safety profile.


Subject(s)
Antipsychotic Agents/blood , Antipsychotic Agents/therapeutic use , Clozapine/blood , Clozapine/therapeutic use , Drug Resistance , Schizophrenia/drug therapy , Administration, Oral , Adult , Anticonvulsants/adverse effects , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Antipsychotic Agents/pharmacokinetics , Caffeine/adverse effects , Case-Control Studies , Central Nervous System Stimulants/adverse effects , Chi-Square Distribution , Chromatography, High Pressure Liquid , Clozapine/administration & dosage , Clozapine/adverse effects , Clozapine/pharmacokinetics , Cross-Sectional Studies , Drug Interactions , Drug Monitoring/methods , Female , Food-Drug Interactions , Humans , Least-Squares Analysis , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Psychiatric Status Rating Scales , Risk Factors , Schizophrenia/blood , Schizophrenia/diagnosis , Schizophrenic Psychology , Spectrophotometry, Ultraviolet , Treatment Failure , Valproic Acid/adverse effects
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