Psychopharmacological Agents Research Articles

Chapter 25 - The psychopharmacology of catatonia, neuroleptic malignant syndrome, akathisia, tardive dyskinesia, and dystonia

Although highly prevalent, motor syndromes in psychiatry and motor side effects of psychopharmacologic agents remain understudied. Catatonia is a syndrome with specific motor abnormalities that can be seen in the context of a variety of psychiatric and somatic conditions. The neuroleptic malignant syndrome is a lethal variant, induced by antipsychotic drugs. Therefore, antipsychotics should be used with caution in the presence of catatonic signs. Antipsychotics and other dopamine-antagonist drugs can also cause motor side effects such as akathisia, (tardive) dyskinesia, and dystonia. These syndromes share a debilitating impact on the functioning and well-being of patients. To reduce the risk of inducing these side effects, a balanced and well-advised prescription of antipsychotics is of utmost importance. Clinicians should be able to recognize motor side effects and be knowledgeable of the different treatment modalities.

Subduing the Green-eyed Monster: Bridging the Psychopharmacological and Psychosocial Treatment Perspective in Understanding Pathological Jealousy.

Human being is not spared from a broad-ranged emotional state, including being jealous. Jealousy has both affective-cognitive and behavioural-evaluative dimension where the person perceives, or experiences a real threat on a valued relationship. As this complex emotion becomes irrational and not amenable to reason, it later transforms into a dangerously 'green-eyed monster'. This perilous situation which is viewed as pathological jealousy is a form of delusion, which is maintained by a fixed and false reasoning in an originally entrusted intimate relationship. Pathological jealousy is equally prevailing among both gender, and with a greater ubiquity among the geriatric population. The role of dopamine hyperactivity in the fronto-parietal-temporal region was implicated, with the anatomical mapping of the ventromedial prefrontal cortex (vmPFC), cingulate gyrus (CG), and amygdala involvement in the context of the disease's neurobiology. The etiology of pathological jealousy includes major psychiatric disorders, i.e. delusional disorder, schizophrenia, mood disorder, organic brain syndrome, and among others, the drug-induced psychosis. The role of relationship issues and psychodynamic perspective, i.e. psychological conflicts with dependence on a romantic partner, and low self-esteem are involved. Pathological jealousy inherits high-risk forensic psychiatry entanglement, which may warrant intensive intervention, including hospital admission and antipsychotic treatment. Treatment options include an early recognition, managing underlying neuropsychiatric disorders, psycho education, cognitive psychotherapy, and choosing an effective psychopharmacological agent. The management strategy may also resort to a geographical intervention, i.e. separation between both persons to complement the biological treatment.

Co-Morbid Erectile Dysfunction (ED) and Antidepressant Treatment in a Patient - A Management Challenge?

Throughout the world, antidepressants (AD) and phosphodiesterase-5 inhibitors (PDE-5i) are the commonly prescribed psychopharmacological agents for treating patients with co-morbid mental health problem and sexual dysfunction (SD). The serotonergic and noradrenergic ADs, although effective, are not without any SD adverse-effects, especially erectile dysfunction (ED). ED is a failure to obtain a satisfactory erection for rewarding sexual coitus during the phases of male's sexual arousal. It is recognized as an important reason why non-adherence to treatment was observed in patients who were on AD. AD intervention caused remission to some of the pre- treatment psychopathology of ED. However, in many patients, AD potentially magnified the unwanted sexual sideeffects. This made the situation challenging for the mental health professional. These challenges are based on the complexity of ED, its etiology and the associated risk factors, which further add to its AD side-effect. The neuro-psychopharmacological basis for AD treatment selection was deliberated. Bio-psycho-social interventions are recommended at two pivotal stages. Firstly, a step should be taken for proper assessment (e.g. detailed history, psychosocial and laboratory investigations); and identify few modifiable risk factors for ED and associated mental health issues. Secondly, with guidance of an algorithm pathway, a practical intervention should include strategies such as dose reduction, augmentation or changing to an AD with lesser or no sexual adverse-effects. It is recommended that bupropion and mirtazepine to be prescribed when patients develop adverse sexual effects with serotonin selective reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA). Few suggestions which may be borne in mind are revising sexual scripts and improving sexual techniques, life-style modifications, psychotherapy and other nonpharmacological approaches which may be beneficial to both patients and their partners.

Schizophrenia and Nicotine Dependence: What Psychopharmacological Treatment Options are Available for the Duo Perturbationes?

Nicotine dependence has progressively become a foremost community health interest in both the developed and developing nations due to the economic burden and health-related problems. Smoking was significantly higher among patients with schizophrenia in comparison to the general population. Nicotine dependence is not only associated with public stress, but among patients with schizophrenia, smoking brings major challenges to the management. Nicotine may diminish the therapeutic efficacy of the bioavailability of the psychopharmacological agents in-vivo. These duo perturbations, i.e. two clinical conditions co-existed may prevent psychotic symptoms remission among patients suffering from schizophrenia who smoke at the same time. The aim of this review was to highlight the role of pharmacological treatment options and strategies for patients with nicotine dependence in schizophrenia with emphasis on the underlying neurobiological process. The role of nicotine replacement therapy, i.e. norepinephrine-dopamine reuptake inhibition (NDRI) e.g. bupropion and selective partial agonist of α4β2 and full α7-nicotinic acetylcholine receptor e.g. varenicline was deliberated. An ideal choice of drug targets for patients with schizophrenia with nicotine dependence is pivotal to foster a better therapeutic alliance.

Penolakkan Sekolah pada Anak dengan Gangguan Cemas Sosial

School refusal happens in children often present with complaints that are different from adults. Parents might misinterprete their children as misbehaving when these misbehaves are actually the symptoms of anxiety in children, hence the under-detection of the anxiety. One form of anxiety in children that might lead to school refusal is the social anxiety disorder in childhood. We conducted a case study on a female child in the outpatient Psychiatry department, Sanglah General Hospital. She presented with a chief complaint of school refusal. After clinical, mental, and additional asseessment with Pediatric Symptom Chekclist-17 (PSC-17), Hamilton Depression Rating Scale (HDRS), Hamilton Rating Scale of Anxiety (HRSA) and The Spence Children’s Anxiety Scale (SCAS), diagnosis of childhood social anxiety disorder was revealed. The patient was managed with psychopharmacological agent Selective Serotonin Reuptake Inhibitor (SSRI) and Cognitive Behavioral Therapy (CBT). A decrease in anxiety and cessation of the school refusal was reported about 4 weeks later. The multidisciplinary holistic management required collaboration among medical personnels, parents, other people in the child’s social circle, teachers in addition to the psychopharmacological agent and psychotherapy.Â

Monitoring adverse drug reaction of psychopharmacological agents: a pharmacovigilance study in tertiary care centre

Monitoring adverse drug reaction of psychopharmacological agents: a pharmacovigilance study in tertiary care centre

Psychopharmacological prescribing practices in pregnancy for women with severe mental illness: A multicentre study

There is little known about real world psychopharmacological prescribing practices in managing pregnant women with severe mental illness (SMI). This study utilised a sample of 535 women with a SMI across two hospitals in Australia. This included women with psychotic disorders, bipolar disorder and a range of non-psychotic disorders. The majority of women with a SMI in pregnancy were prescribed psychotropic medication as part of their management. Furthermore, more than one class of agent was prescribed for 31% of women with psychotic disorders and 30% of women with bipolar disorder. Differences between sites were identified in prescribing practices across the mental disorders. This included the variation in rates of use of multiple agents and pattern of use across pregnancy. This study also identified that women with a SMI had elevated rates of gestational hypertension, gestational diabetes mellitus, smoking and obesity in pregnancy and neonates admitted following delivery compared with the Australian average. These findings suggest that studies that examine associated risks for severe mental disorders or their treatments on pregnancy and infant outcomes should take into account the prescribing practices including the likelihood of exposure to polypharmacy and a range of potential confounding co-morbidities and exposures. The discrepancies in reported findings for pregnancy and infant outcomes following use of antipsychotic and mood stabiliser agents such as lithium may be at least partially accounted for by the complexity of multiple exposures that includes use of multiple psychopharmacological agents, co-exposures such as smoking and co-morbid conditions such as obesity.

The Use of Statins for Antipsychotic Augmentation in Schizophrenia: Examination of Meta-Analyses With Flawed Methods and Conclusions.

A very large number of psychopharmacologic agents have been trialed as antipsychotic augmentation strategies for the improvement of positive, negative, mood, cognitive, and other symptoms of schizophrenia; statins are one among these. Two very recent meta-analyses examined data on statin augmentation from 5 to 6 randomized controlled trials (RCTs) in the field. One meta-analysis found that statins were superior to placebo for the improvement of total scale and general psychopathology subscale scores on the Positive and Negative Syndrome Scale; statins were no better than placebo for positive and negative subscale outcomes. The other meta-analysis, in contrast, found that statins were superior to placebo for the improvement of positive and negative subscale scores but were no better than placebo for total scale and general psychopathology subscale outcomes. Both meta-analyses were associated with serious flaws such as the combination of studies conducted in contrasting stages of illness, the combination of change and endpoint scores in the same analysis, and the use of numbers that were prima facie incorrect. The first take-home message is that clinicians who read meta-analyses for guidance on how to better treat patients and researchers who read meta-analyses with a view to citing these in their papers both need to exercise due diligence to determine whether what they are reading is valid or flawed. Because this could be a difficult task, journal editors and reviewers need to take more care during manuscript screening and processing than they appear to be doing at present. The second take-home message is that the consideration of statin augmentation is based on very few RCTs and the differences between trial drug and placebo in these RCTs are mostly so small as to be clinically not worth considering.

Should patients be informed about the side effects of psychotropic drugs? According to us: Yes

BackgroundIn our daily clinical practice, we observe that patients who were informed about the probable side effects of any medication experience less side effects. For this reason, we decided to examine this in a systematic investigation. MethodsWe divided patients into two groups, the informed and uninformed one about side effects of the drugs. During the control examination, tolerability of the drugs given was questioned in detail. ResultsAt the end of one month, the mean total UKU score was statistically significantly lower in patients from the informed group compared to that of the uninformed one (p < 0.05). The proportion of patients who discontinued the drug during the one month-period was statistically significantly higher in the uninformed group compared to informed group 9% in the informed group vs. 25% in the uninformed group) (p < 0.05). ConclusionsFinally, we found that giving information about the side effects of a psychopharmacological agent seems to be useful and to provide beneficial effects on the tolerability of the drug, independent of the kind of psychotropic agent.

Hand functions in patients with schizophrenia: A clinical comparison with bipolar disorder and healthy subjects

ObjectiveFailure to achieve expected level of motor functioning may be a significant contributor to social withdrawal and further attenuation of life quality in patients with schizophrenia. Hand functioning is one of the most crucial entities in that manner. This study aimed to reveal this question by means of comparing patients with schizophrenia and bipolar disorder who are receiving similar antipsychotic psychopharmacological agents along with healthy control subjects. Methods99 patients with schizophrenia were compared to 40 patients with bipolar disorder matched according to the received pharmacotherapy comprising similar antipsychotics and 81 medication-free socio-demographically matched healthy control subjects. The materials were Hand Functional Index (HFI), Duruoz Hand Index (DHI), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS) along with clinical characteristics. ResultsDifference in total scores of DHI and HFI between schizophrenia, bipolar disorder and control groups were extremely significant (p < 0.001). Further post-hoc subgroup analysis revealed that patients with schizophrenia demonstrated higher scores of HFI indicating worse performance when compared to both bipolar disorder and control group. Significantly higher scores of DHI in patients with schizophrenia than healthy controls were noted. ConclusionIndependent from the impact of the medication use, impairment in hand functions was found to be more frequently seen in schizophrenia when compared to patients with bipolar disorder and healthy subjects. It is evident that hand function impairment is seen independent from psychopharmacological side effect, and is recommended to be assessed as a possible preventable and retractable manifestation of schizophrenia.

The Role of Atypical Antipsychotics in Sexuality: Road to Recovery in Schizophrenia.

Sexuality is an important dimension in human beings as a form of expression of individuality. For many decades, sexual functioning has been a neglected area among patients suffering from schizophrenia. It was a presumption that patients with schizophrenia could be asexual and this could be secondary to overwhelming situations of delusion, hallucination, hostility and negative symptoms among others. The deficient in sexual functioning are due to innate factors, i.e. negative symptoms (apathy, avolition and amotivation) and also as a result of prefrontal dysfunction, i.e. inability to plan and execute meaningful relationship. Adverse effects of the psychopharmacological agents, especially the typical antipsychotics, e.g. dystonia, excessive sedation and hyperprolactinemia may interfere with patients' sexual activity. In this review, we highlight the neurobiology of schizophrenia in the context of understanding sexual functioning and to integrate the knowledge of dopamine-serotonin neurotransmitter's interaction and the receptors' target. Interventional approaches consist of psychopharmacological and psychosocial interventions. In the perspective of sexuality, we recommend atypical antipsychotic should be placed as the first line treatment for both drug naïve patients and also to patients who are already receiving psychopharmacological agents in consideration for a drug-switch from typical to atypical antipsychotics. Aripiprazole, clozapine, olanzapine and quetiapine exert benefits in terms of sexual functioning recovery due to their atypical mechanism of action. However, the potential adverse effect like metabolic syndrome should be adequately managed to prevent negative consequences. Psychosocial interventions, i.e. psychoeducation, destigmatization, supportive psychotherapy and psychiatric rehabilitation also play a crucial role in the management. In conclusion, restoration of sexual function is an achievable recovery target in patients with schizophrenia through these biopsycho- social interventions.

Dermatologic Effects of Psychopharmacologic Agents in the Pediatric Population

Dermatologic Effects of Psychopharmacologic Agents in the Pediatric Population

The role of meta-analyses and umbrella reviews in assessing the harms of psychotropic medications: beyond qualitative synthesis.

ὠφελέειν, ἢ μὴ βλάπτειν (Primum non nocere) - Hιppocrates' principle should still guide daily medical prescribing. Therefore, assessing evidence of psychopharmacologic agents' safety and harms is essential. Randomised controlled trials (RCTs) and observational studies may provide complementary information about harms of psychopharmacologic medications from both experimental and real-world settings. It is considered that RCTs provide a better control of confounding variables, while observational studies provide evidence from larger samples, longer follow-ups, in more representative samples, which may be more reflective of real-life clinical scenarios. However, this may not always hold true. Moreover, in observational studies, safety data are poorly or inconsistently reported, precluding reliable quantitative synthesis in meta-analyses. Beyond individual studies, meta-analyses, which represent the highest level of 'evidence', can be misleading, redundant and of low methodological quality. Overlapping meta-analyses sometimes even reach different conclusions on the same topic. Meta-analyses should be assessed systematically. Descriptive reviews of reviews can be poorly informative. Conversely, 'umbrella reviews' can use a quantitative approach to grade evidence. In this editorial, we present the main factors involved in the assessment of psychopharmacologic agents' harms from individual studies, meta-analyses and umbrella reviews. Study design features, sample size, number of the events of interest, summary effect sizes, p-values, heterogeneity, 95% prediction intervals, confounding factor adjustment and tests of bias (e.g., small-study effects and excess significance) can be combined with other assessment tools, such as AMSTAR and GRADE to create a framework for assessing the credibility of evidence.

An Additive Mix? Acute Urinary Retention in a Patient With Benign Prostatic Hyperplasia Treated With Suboxone, Lurasidone, and Trazodone.

Treatment of psychiatric patients is frequently complicated by medical comorbidities, complex pharmacologic regimens, and side effects occurring secondarily to those regimens. Acute urinary retention is an infrequently discussed side effect of such regimens. This report describes the development of acute urinary retention (AUR) in a 60-year-old man with a history of benign prostatic hyperplasia. The patient developed AUR during treatment with combination buprenorphine/naloxone, trazodone, and lurasidone. We discuss the potential relationship of these agents to the development of this patient's AUR, the complicated neurochemical dynamic of the voiding process, and the pathologic consequences that psychotropic agents can have on that process.

USE OF CLUSTER ANALYSIS FOR EVALUATION OF ACUTE POISONING REHABILITATION TREATMENT EFFICIENCY

Observations of 153 patients admitted to the toxicological department of the N.V. Sklifosovsky Research Institute for Emergency Medicine after severe poisoning with psychopharmacological agents (36), cauterizing fluids (67) and neurotoxicants (drugs of the opium group, ethanol and psychopharmacological agents) (50) were summarized. A hierarchical cluster analysis was used to assess the systemic response of the body to a chemical injury of varying severity and the treatment used. The data obtained shows that taking into account the complexity of the response of homeostasis indicators to various impacts the characteristics of the shifts to the manifestations of mentioned acute poisonings and treatment measures in the rehabilitation period with the use of cluster analysis should be evaluated using data that indicates changes in the strength of the bonds (proximity levels) both for individual indicators and for the values of intrasystemic connections in individual systems and between them. Cluster analysis provides an opportunity to obtain new information about the pathogenesis of the studied poisonings and also has predictive capabilities. Changes in the assessed indicators obtained by cluster analysis correspond to their shifts in the process of one dimensional analysis, positive results of treatment (reduction of treatment duration) and, therefore, are recommended for practical use.

Mifepristone as a Psychopharmacologic Agent: Consideration of Efficacy, Plasma Levels, and Mechanism of Action

Mifepristone as a Psychopharmacologic Agent: Consideration of Efficacy, Plasma Levels, and Mechanism of Action

A Systematic Review of Atypical Antipsychotics in Chronic Pain Management: Olanzapine Demonstrates Potential in Central Sensitization, Fibromyalgia, and Headache/Migraine.

Many psychopharmacologic agents are used as primary or adjuncts in pain management. Atypical antipsychotics (AAs) have also been used as adjuncts in pain management regimens in a variety of manners; however, their efficacy in this capacity is unclear. A systematic review of all studies examining AA use for pain was conducted. Three literature databases were utilized to search for word combinations of "pain" and a variety of commonly prescribed AAs ie, (olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, clozapine, paliperidone, iloperidone, lurasidone). Articles chosen for review included retrospective analyses, randomized control trials, and case series/reports. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram illustrates the study selection process. Olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone are the only AAs with published studies in pain management. Among these, olanzapine and quetiapine have the most studies (11 and 6, respectively). Olanzapine shows preliminary and consistent efficacy in fibromyalgia and headache/migraine, although only 1 study was a randomized controlled trial with level I evidence of efficacy. Other AAs eg, (quetiapine) fail to demonstrate efficacy in pain syndromes and/or lack robust study designs. Few studies have been conducted to evaluate the analgesic effects of AAs. The collective findings of multiple studies evaluating olanzapine in pain syndromes suggest a high, yet preliminary level of evidence of efficacy, warranting prospective studies in various pain syndrome contexts. Pharmacological mechanisms of AA action are elaborated, and the findings of this review are discussed. Risk and benefits of using AAs in chronic pain are described, and investigational implications and future directions are explored.

Understanding the Pathophysiology of Premature Ejaculation: Bridging the Link between Pharmacological and Psychological Interventions.

Premature ejaculation (PE) is one of the commonest male sexual dysfunctions. It is characterized by ejaculation which occurs before or soon after vaginal penetration, which causes significant psychological distress to the individual, and his partner. The exact cause of PE is still unknown but several mechanisms are proposed, and these involve complex interactions of neurophysiological, psychosocial, and cognitive factors. We discuss the role of serotonin, nitric oxide, phosphodiesterase enzymes and other neurotransmitters. Treatment of PE tends to co-occur with other sexual difficulties, especially erectile dysfunction (ED). Treatment with selective serotonin reuptake inhibitors (SSRIs) and Dapoxitene are also discussed in detail. The treatment strategy requires a comprehensive holistic approach incorporating both combination of psychopharmacological agent and cognitive-behavioral therapy (CBT). The present review highlights the integration of the hypothalamic-neural and reverberating emotional circuit and discusses the etiology and treatment for patients with PE.

T229. ANTIPSYCHOTIC DRUG USE AND THYROID FUNCTION IN PATIENTS WITH SEVERE MENTAL DISORDERS

BackgroundAltered levels of free Thyroxin (fT4) and Thyroid Stimulating Hormone (TSH) have been associated with severe mental disorders and the use of antipsychotic drugs. Still, there is a lack of studies systematically investigating commonly prescribed antipsychotic drugs and thyroid function. We investigated the association of antipsychotic drugs and thyroid hormones levels in patients with severe mental disorders and compared thyroid function tests between patients and healthy controls under real-life conditions.MethodsWe included 1345 patients with schizophrenia or bipolar disorders and 989 healthy controls from the on-going Thematically Organized Psychosis (TOP) study, recruiting participants between 18–65 years of age in and around Oslo, Norway. All patients underwent a thorough clinical investigation including diagnostic evaluation, somatic screening and assessment of medication data. Serum drug concentrations were measured. Plasma levels of fT4 and TSH were measured in patients and healthy controls, and thyroid status was determined based on the combined hormone levels. Participants with known thyroid function disorders (N=28) were excluded. Mann-Whitney U tests and chi-square tests were performed for comparison between groups. For evaluation of influence from antipsychotics, multiple linear regression analyses were performed, adjusting for patient/control status, age, sex and use of other psychopharmacological agents. Associations with the use of olanzapine, quetiapine, aripiprazole or risperidone in monotherapy were analyzed in a subsample of patients (N=480), adjusting for age, sex and diagnosis. Spearman correlation analyses were performed for hormone levels and drug serum concentrations.ResultsWe found significant lower levels of fT4 (median 13.70 vs 14.00, p<0.001) and higher levels of TSH (median 1.92 vs 1.57, p<0.001) in patients compared to healthy controls. A significant difference between patients and controls in occurrence of hyper- and hypothyreosis was observed (p<0.001), with more than three times as many patients compared to controls with hypothyroid status (11.1% vs 3.4%), and a doubling of hyperthyroid status (2.3% vs. 1.2%). Use of antipsychotics was significantly associated with lower fT4 level (p=0.001), but not with the TSH level. We also found significant associations between lower fT4 level and current use of quetiapine (p=0.005) and olanzapine (p=0.018), but again no significant associations were found with TSH level. No significant correlations were found between drug serum concentrations and fT4 or TSH. In the regression analyses we also observed that female sex and increasing age was associated with lower levels of both fT4 and TSH.DiscussionIn this large, cross-sectional study we found significant differences in thyroid hormone levels between patients with schizophrenia and bipolar disorders and healthy controls, and our data indicate a notable prevalence of undetected deviant thyroid function in the patient population. There was a significant association between fT4 level and the use of antipsychotics, particularly with the use of quetiapine and olanzapine. This suggests a possible contribution to altered thyroid hormone levels from the use of commonly prescribed antipsychotic agents. These findings call for renewed attention towards the role of thyroid function in severe mental disorders and the associations with antipsychotic drugs.

The Clozapine Clinic: A Model of Integrated Care

Introduction: A significant proportion of individuals with psychotic illness are either refractory to, or intolerant of, standard antipsychotic pharmacotherapy. There is currently only one medication available with proven effectiveness in this population. Clozapine while providing a superior response rate requires significant physical health care monitoring both before and during treatment. The medication requires weekly hematologic monitoring and intensive metabolic screening. Methods: A site was selected for establishment of a new Clozapine Clinic to provide services for individuals with treatment refractory psychotic symptoms or individuals with medication side effects deemed to be related to standard antipsychotic medications. Individuals were selected without predetermined exclusion criteria such as age or physical comorbidity. Patients were accepted into the Clozapine Clinic with a combination of physical health and mental health assessments. The Clozapine Clinic was fortunately located in close proximity to a County Primary Care Clinic and County Tertiary Care Hospital, both of which were helpful in obtaining baseline physical health assessments and diagnostic tests and concurrent hematologic and metabolic laboratory monitoring Results: A new Clozapine Medication Support service line was established using a collaborative care model with existing County facilities. At total of 10 new and established individuals were enrolled into the Clozapine Clinic, with weekly, biweekly and monthly psychiatric and physical health monitoring. The Clozapine Clinic continues to receive referrals for individuals in need of complex care with this unique psychopharmacologic agent. Conclusions: Clozapine pharmacotherapy for treatment resistant psychotic symptoms provides a model for integrated care in this population. Using a collaborative relationship and employing integrated care principles as the model, the complex care of new and established Clozapine patients was provided at an existing County Mental Health Clinic. Weekly hematologic and metabolic monitoring was achieved by partnering with the affiliated hospital laboratory in order to provide rapid, same day results. A dedicated Clozapine Clinic Nurse was employed to provide the coordination of physical health assessments, psychiatric evaluations and laboratory monitoring. In less than a year, the Clozapine Clinic services at this clinical site were expanded to approximately 10 individuals, with additional individuals awaiting entry. Clozapine pharmacotherapy for treatment refractory psychiatric illness is vastly underutilized in large part due to the complexity in coordination of physical health and mental health needs. This underutilization leads to high levels of morbidity and mortality in the psychiatric population. Implications for Integrated Care Practice: Since a significant percentage of patients with chronic psychotic illness are either intolerant or refractory to standard antipsychotic medications, Clozapine remains the only effective agent available. However, with its significant need for monitoring of physical health side effects, integrated care models of treatment provide the most cost effective, efficient and comprehensive model for addressing the whole person health care needs of this special population. Integrated Care models represent the solution to the underutilization of Clozapine pharmacotherapy in treatment resistant populations.