EDITORIAL
Year : 2022 | Volume
: 27 | Issue : 1 | Page : 1--7
Managing medical comorbidities in clinical practice: Should psychiatrists do more for their patients?
Sandeep Grover
Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Correspondence Address:
Dr. Sandeep Grover
Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012
India
How to cite this article:
Grover S. Managing medical comorbidities in clinical practice: Should psychiatrists do more for their patients?.J Mental Health Hum Behav 2022;27:1-7
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How to cite this URL:
Grover S. Managing medical comorbidities in clinical practice: Should psychiatrists do more for their patients?. J Mental Health Hum Behav [serial online] 2022 [cited 2023 Jun 4 ];27:1-7
Available from: https://www.jmhhb.org/text.asp?2022/27/1/1/353752 |
Full Text
Introduction
It is now increasingly recognized that comorbidity in persons with mental illnesses is a rule rather than an exception. The National Comorbidity Survey Replication study suggests that about two-thirds (68%) of adult patients with various mental disorders have a physical illness, and 29% of adults with medical conditions have a mental disorder.[1] Current understanding also suggests that many chronic physical diseases and mental disorders share common risk factors such as childhood adversities, stress, and various environmental risk factors such as poverty, all of which give rise to adverse health-related behaviors and outcomes, such as obesity, sedentary lifestyle, and substance use. These, on the other hand, contribute to the development and maintenance of various psychiatric and physical illnesses.[1] These findings suggest that mental health professionals should be well versed with multiple physical diseases, their treatment, and their interaction with mental illnesses and psychiatric treatments. Despite the high rate of comorbidity between the mental and physical conditions, most drug trials evaluating newer psychotropics prefer to include only patients without any comorbid psychiatric or physical illnesses. This often complicates the matter further for the mental health professionals in selecting various psychotropics in routine clinical practice when encountering a patient with comorbid physical diseases.
Currently, most of the clinical psychiatric practice occurs in general hospital settings and multispecialty hospitals. This is true for government settings and also in the private sector. This facilitates the referral of patients with mental illnesses to specialists and super-specialists for advice about their physical health issues. However, there are many barriers to appropriate physical health care for patients with mental illnesses. First, patients with mental illnesses, especially those with severe mental disorders, are often discriminated against by physicians. Due to the same, often they receive suboptimal care, especially when they present with acute medical or surgical emergencies. Second, when patients with mental illnesses are referred to physicians, they often prescribe medications that lead to drug interactions and duplication of prescriptions. This, at times, leads to cumulative side effects or reduction in the efficacy of the ongoing psychotropics. Third, although most physicians prescribe medications for the underlying health condition, much less emphasis is given to nonpharmacological measures. Finally, many a time, patients are also reluctant to visit different physicians and request mental health professionals to treat the underlying physical morbidity too.
The most common causes of mortality among patients with severe mental disorders are cardiovascular diseases, cancers, and suicide, with patients with mental disorders dying about 20 years earlier than the general population.[2] This fact is further complicated by the fact that over the years, the prescription of antipsychotics has shifted from typical antipsychotics to atypical antipsychotics,[3] which are more often associated with metabolic disturbances.[4] This mortality pattern suggests that mental health professionals should make efforts to reduce the risk for the development of cardiovascular diseases.
All these warrant that psychiatrists should take up the responsibility of managing the physical illnesses of their patients. This does not mean that they should not refer the patients with mental illnesses to specialists/super-specialists for the physical health issues; rather, this should be understood as psychiatrists improving their knowledge about managing various physical ailments to carry out effective consultation-liaison. All psychiatrists have to remind themselves that they are physicians too!
For psychiatrists to be effective physicians, it is crucial to follow the ten basic commandments [Table 1]. In the subsequent section, I will elaborate on the same. When discussing the Ten Commandments, I would use the example of metabolic disturbances, which are reported to be associated with cardiovascular disease. However, these principles should be considered across all the physical health comorbidities.{Table 1}
Regularly Screen their Patients for Medical Illnesses
When evaluating patients, besides focusing on the psychiatric history, the mental health professionals should give equal importance to the evaluation of medical history, especially metabolic problems like obesity, diabetes mellitus, hypertension, and features of dyslipidemia. The clinicians should also give due importance to evaluating the family history of obesity, diabetes mellitus, hypertension, and other metabolic disturbances. Besides this, due preference should also be given to assessing eating patterns, nutritional status, physical activities, and exercises. A detailed physical examination can also provide important information about various physical illnesses. Hence, psychiatrists should always perform a thorough physical examination of their patients to ascertain different physical ailments. Psychiatrists often tend to prescribe psychotropics to patients with mental illnesses without carrying out baseline investigations. The psychiatrists should refrain from such practices and carry out essential routine investigations (hemogram, liver function test, renal function test, serum electrolytes, electrocardiogram, etc.) in all patients whenever feasible before prescribing. Other investigations should also be considered as per the need before prescribing to minimize the risk of missing out on physical illnesses. The consensus statement of the American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; and North American Association for the Study of Obesity recommend that before prescribing antipsychotics, clinicians should collect information about Personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease.[5]
Additionally, it is recommended that all patients considered for antipsychotic prescription should be assessed for weight, waist circumference, and blood pressure; the investigations should include assessment of fasting blood glucose levels and lipid profile.[5] The patients on atypical antipsychotics should also be monitored for various anthropometric parameters (height, weight, and waist circumference), fasting blood glucose levels, and fasting lipid profile.[5] Elderly patients considered for antidepressant prescription should be evaluated for serum sodium, as the most commonly prescribed antidepressants, i.e., selective serotonin reuptake inhibitors, are known to cause hyponatremia.[6] Similarly, all the patients considered for lithium, valproate, and clozapine should undergo the recommended set of investigations. Neuroimaging should be considered in patients with neurological signs or symptoms, those with a preexisting neurological condition or brain pathology, if a patient has a significant change in clinical presentation, among those with a family history of neurological disorders, presence of the history of head injury, presence of seizures, new or first onset illness, acute onset illness, delirium, recent or progressive cognitive decline, and before electroconvulsive therapy.[7],[8] Regular screening of patients for physical diseases is expected to help identify the physical conditions previously not diagnosed, influence the selection of psychotropics, and in early intervention for managing metabolic disturbances.
Closely Liaise with Physicians
When referring their patients to various specialists/super-specialists, the psychiatrists should closely liaise with them to clearly state the reason for referral and what they want from the physicians. This can be facilitated by having direct communication with the physicians, as this can reduce the communication gap and enhance psychiatrists' knowledge concerning physical illnesses and their management. Direct contact can also help discuss drug interactions and cumulative side effects of the whole prescription, reduce the duplicacy of medication and enhance rational pharmacotherapy.
Have a Better Understanding of Psychotropics with a Lower Risk of Physical Illnesses
When prescribing, the psychiatrists need to remember that although there may not be much difference in the efficacy of various psychotropics, they differ in their side effect profiles. The side effects of major concerns include metabolic side effects (i.e., weight gain, dyslipidemia, diabetes mellitus, and hypertension), electrolyte disturbances (hyponatremia), QTc prolongation, extrapyramidal side effects, sexual dysfunction, seizure, etc., Understanding side effects becomes much more important when prescribing to patients with preexisting physical illnesses, those at risk for developing physical illnesses due to risk factors, or those on other medications (non-psychotropics) that can have similar side effects. The initial selection of a drug to treat a particular psychiatric disorder should consider the medical illness or the risk of developing medical diseases. The psychiatrist should use medications that have the least or no potential to cause medical complications. For example, if antipsychotic medication is to be prescribed, drugs like ziprasidone or aripiprazole should be preferred over olanzapine. If the psychiatrist likes to start medication with possible metabolic/medical complications, they should educate the patients about possible metabolic/medical complications and monitor them for early identification and management. The psychiatrist should also be prepared to switch the medications if the patient develops medical problems due to psychotropics. For example, guidelines/recommendations suggest that a change in antipsychotic should be considered if the patient gains 5% or more body weight; and if a patient develops worsening glycemia or dyslipidemia when on antipsychotic therapy, and switching to an atypical agent that has not been associated with significant metabolic risk should be considered.[5]
Improving the Knowledge about Risk Factors for Specific Side Effects and Medical Illnesses
Certain side effects of psychotropics, such as hyponatremia and QTc prolongation, are not seen in all patients. These side effects become more apparent in the presence of certain vulnerability factors and concomitant medications. For example, older age, female gender, bradycardia, left ventricular failure, liver dysfunction, electrolyte disturbances like hypokalemia, hypomagnesemia, and hypocalcemia can increase the risk of QTc prolongation.[9] Further concomitant use of antiarrhythmic (Quinidine, antimicrobial Levofloxacin, ciprofloxacin, clarithromycin, ketoconazole, etc.), and certain other medications can also increase the risk of QTc prolongation.[9] Accordingly, it can be said that the overall risk of QTc prolongation in an index patient will be influenced by cumulative risk factors and not a psychotropic medication. Similarly, risk factors for seizures,[10] hyponatremia[6] and other side effects have been noted. The knowledge about risk factors will not only help in choosing a medication but also influence the use of prophylactic agents to counter the side effect and frequency and parameters to be monitored when the patient is on the particular medication.
Similarly, an understanding of the risk factors for cardiovascular disease (advancing age, high total serum cholesterol levels, high non-high-density lipoprotein cholesterol (HDL-C) level, high low-density lipoprotein cholesterol (LDL-C) levels, diabetes mellitus, hypertension, chronic kidney disease, smoking, family history of cardiovascular disease),[11] dyslipidemia, hypertension, and diabetes mellitus is also crucial from the perspective of prevention, early identification, and management of metabolic disturbances. This understanding can also improve the selection of psychotropics.
Improve Knowledge about Medications used for Various Physical Illnesses to Minimize the Cumulative Side-effects
Although all the psychiatrists are medical graduates, as they reach the postgraduate level and progress further in the clinical practice, they fail to keep themselves updated about the medications used for various physical illnesses. Improving understanding of the side effects of drugs used for physical diseases can help reduce the cumulative side effects.
Have Knowledge about Behavioral Measures Found to be Effective for the Management of Various Medical Illnesses
Mental health professionals have the edge over physicians in implementing behavioral measures for mental and physical health conditions. It is now well known that wellbeing programs, cognitive behavior therapies, psychoeducation, and weight management (physical exercise, dietary measures) are beneficial in managing various metabolic disturbances such as hypertension and diabetes mellitus. There is a large database on this account, and mental health professionals should implement all these measures to improve the overall outcome of the ongoing physical illnesses and prevent the emergence of physical diseases in their patients. Championing non-pharmacological efforts for various physical ailments can improve the cross-referral of patients from other physicians, who often do not have time and adequate knowledge to carry out these interventions.
Have an understanding of the diagnosis and management of medical illnesses/metabolic disturbances
Considering the high prevalence of comorbid obesity, hypertension, and diabetes mellitus, mental health professionals must be well versed in managing these conditions.
The first step in this direction is diagnosis. There are different cutoffs for defining obesity in different ethnic groups, with cutoffs for the south-Asian population being 25 kg per meter square, which is much lower than the 30 kg per meter square for the western population.[12] Psychiatrists are often unaware of these lower cutoffs and do not initiate treatment or prescribe medications that can worsen the same.
For psychotropic-associated weight reduction, different agents have been recommended. However, the maximum level of evidence is present for metformin. Evidence suggests that metformin is associated with significant weight reduction; however, the response is heterogeneous, and the weight loss is only modest. It is important to note that metformin also has a significant beneficial impact on some of the lipid and glucose parameters. However, it is essential to note that the evidence for the role of metformin in preventing antipsychotic-induced weight gain is inconclusive, and it is not recommended for this purpose. It is usually started in the dose of 500 mg twice daily and titered upward (maximum 2000 mg/day) as needed. The clinicians should remember that long-term use of metformin can lead to Vitamin B12 deficiency, and neuropathy may result from chronic vitamin malabsorption. Use of metformin should be avoided in patients with hepatic impairment (risk of lactic acidosis), in patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2; and initiation is contraindicated and among those with eGFR 30–45 mL/min/1.73 m2. When using metformin, the patients should be asked to abstain from alcohol, as this is associated with an increased risk of lactic acidosis. Patients on metformin should be periodically monitored for renal functions at baseline and then at least annually.[13]
Other commonly used agents for the management of antipsychotic-associated weight gain include topiramate, a glutamatergic inhibitor. It is used in 100–250 mg/day doses and has been shown to have a beneficial effect on both prevention and reduction in antipsychotic-associated weight gain. However, topiramate has no helpful role in the lipid profile.[14]
Many other agents, including betahistine, have been evaluated to manage antipsychotic-associated weight gain, but the literature is limited.
The prevalence of hypertension in the Indian population has been estimated to be 29.8%.[15] Some of the issues to be understood concerning hypertension in India include: it has an onset early in life, a higher prevalence in the urban population compared to the rural population, and the clustering of multiple cardiovascular risk factors. It is also noted that there is high seasonal variation in the blood pressure, and over the years, there has been an increase in the average blood pressure in the general population. Further, poor blood pressure control is associated with early hypertension-mediated organ damage.[15]
For hypertension, different cutoffs are given for the adult population and those in other age groups. For the diagnosis of hypertension, the clinicians should not rely on a single blood pressure reading in the outpatient setting. Before starting medications, it may be essential to monitor the blood pressure at home/in non-healthcare settings and ambulatory blood pressure. At times, patients may have high blood pressure in the clinic but not in other locations and vice-versa. The presence of high blood pressure recordings in the clinic setting but absence in different settings is understood as white-coat hypertension, and this may not require initiation of medications. Patients with white coat hypertension may benefit from lifestyle modification and blood pressure monitoring.[15],[16] The non-pharmacological measures as part of lifestyle modifications should include weight reduction, a heart-healthy diet, low sodium intake, an increase in potassium intake if the levels are low, an increase in physical activity, a reduction in alcohol intake, and avoidance of smoking.[15],[16]
On the other hand, the absence of recordings of high blood pressure in the clinic setting but the presence of high blood pressure in different locations may be understood as masked hypertension, which may require the initiation of medications. The presence of high blood pressure irrespective of the assessment setting should indicate definite evidence of hypertension. In case of hypertension, the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines recommends that all patients with hypertension should be investigated (hemogram, fasting blood glucose levels (optional), lipid profile, serum creatinine levels, estimated glomerular filtration rate, serum sodium, potassium and calcium (optional) levels, thyroid-stimulating hormone levels, urinalysis, electrocardiogram, echocardiogram, estimation of serum uric acid levels, and urinary albumin to creatinine ratio estimation) properly to ascertain the cause of hypertension.[16]
Depending on the stage of hypertension [Table 2], different treatment recommendations are made. Patients with stage-I hypertension should receive lifestyle modification, and the reading should be repeated in 2–3 weeks if the high blood pressure persists, then pharmacotherapy should be instituted. It is to be noted that before starting pharmacotherapy, the blood pressure recordings should be taken in both the arms and in lying and standing postures. In patients with stage-II and III hypertension, a shorter waiting duration should be considered. If the high blood pressure persists, then pharmacotherapy should be started along with the continuation of lifestyle modification. In patients with evidence of hypertension-related organ damage, pharmacotherapy should be instituted early.[15]{Table 2}
In terms of management, Indian hypertension guidelines suggest using angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) as the first-line agents in persons under 60 years. In contrast, in persons older than 60, calcium channel blockers and diuretics are preferred. It is suggested that a significant proportion of the patients may require more than one agent to control blood pressure. When combining different agents, a combination of ACEIs/ARBs with calcium channel blockers is preferred. If the patient requires a third agent, diuretics should be used as the third drug in the combination. While treating hypertension, blood pressure of <130/80 should be the target for those younger than 60 years, and for the elderly, this should be individualized.[15]
India is the diabetic capital of the globe. The Indian Council of Medical Research Guidelines for managing diabetes mellitus suggests that everyone aged >30 years should be screened for diabetes mellitus. Additionally, it suggests that screening may even be done earlier if the person has a family history of diabetes mellitus, is overweight/obese (i.e., has a body mass index of ≥23 kg per meter square, increased waist circumference (>90 cm males, >80 cm females), history of hypertension or receiving treatment for hypertension, history of dyslipidemia, having a sedentary physical activity, history of cardiovascular diseases, history of cerebrovascular disease, history of the polycystic ovarian syndrome and/or acanthosis nigricans, history of gestational diabetes mellitus or macrosomia (i.e., birth weight >3.5 kilograms). Concerning signs and symptoms of diabetes mellitus, besides the classical features (polyuria, polydipsia, and polyphagia), psychiatrists should remember that weight loss may be a feature of diabetes mellitus and any new onset weight loss (especially in the presence of polyphagia) should lead to evaluation for diabetes mellitus. Other clinical features of diabetes mellitus include tiredness, weakness, generalized pruritus, recurrent urinary tract or genital infection, and delayed healing of wounds.[17] Another critical fact to remember is that some patients with diabetes mellitus may be asymptomatic. In terms of diagnosis, a diagnosis of diabetes mellitus should be considered if the patient's plasma glucose level is more than 125 mg/dl or if the random plasma glucose is >200 mg/dl or 2 h postprandial glucose is >200 mg/dl or if the Hba1c levels are >6.5 mg/dl.[17] To manage diabetes mellitus, all patients should receive advice for lifestyle modification. Regarding pharmacotherapy, if the HbA1c is <9 mg/dl, the first-line treatment should be metformin. However, if the HbA1c is more than 9 mg/dl and the patient is symptomatic, then insulin should be considered. If the patient with HbA1c is more than 9 mg/dl and is asymptomatic dual oral hypoglycemic agents should be considered, i.e., metformin plus one of the sulfonylureas or dipeptidyl peptidase-4 inhibitors (i.e., gliptins), or a sodium-glucose cotransporter-2 inhibitor (canagliflozin, dapagliflozin, and empagliflozin). If this does not reduce HbA1c to the targeted levels, then the addition of insulin or a triple oral therapy should be considered.[17]
Dyslipidemia is understood as elevations in lipoprotein cholesterol, including LDL-Cs, non-HDL-C, and triglycerides levels. All these features are associated with a high risk of atherosclerotic cardiovascular disease. A host of medical conditions increase the risk of dyslipidemia.[11]
Antipsychotics and other psychotropics are known to lead to dyslipidemia. Hence, it is essential to monitor the lipid profile. It is recommended that all patients considered to receive antipsychotics should be evaluated for lipid profile. The investigation panel should include an assessment of lipid profile (total cholesterol, HDL-C, triglycerides, LDL-C, and calculated non-HDL-C) at the baseline, and the same should be monitored periodically (ADA, 2004). When carrying out a physical examination, the psychiatrist should also focus on the patient's height and weight (for calculation of BMI), waist circumference, blood pressure, and peripheral and carotid pulses. Additional assessment can involve looking for various xanthomas and xanthelasmas. Based on the associated medical comorbidities, atherosclerotic cardiovascular disease risk scores should be calculated to determine the target level of lipid parameters.[11]
In terms of management, all patients should receive lifestyle modification advice that should focus on dietary modification (consume diets rich in fruits and vegetables, whole grains, legumes, and high soluble fiber, and avoiding processed foods, a reduction in total calories, low salt intake, fats contributing to 25%–35% of the calories intake), increase in physical activity, adequate sleep, reduction in alcohol intake and avoidance of smoking. All patients with dyslipidemia should receive dietary advice. A high LDL-C should be managed with statins until and unless contraindicated. If a patient has high triglyceride levels, the pharmacologic management involves the use of fibrates (reduced by 45%–55%), omega-3 fatty acids (reduced by 20%–45%), and nicotinic acid (niacin) (reduced by 20%–30%). Management of low HDL-C should include niacin, which is also a potent LDL-C-and triglyceride-lowering medication, too.[11]
Have an Understanding of the Psychiatric Side Effects of Other Medications
Many medications used for different physical illnesses cause psychiatric side effects.[18] Accordingly, whenever a patient diagnosed with physical conditions presents with psychiatric manifestations for the first time, the possibility of psychiatric syndrome due to underlying medical illness or drug-induced psychiatric disorder should be considered, besides the independent psychiatric disorder. For example, steroids cause a wide range of psychiatric manifestations (Depression, anxiety, psychosis, mania, delirium, cognitive dysfunction, etc.), and steroids can also lead to worsening underlying mental disorders. Other drugs commonly associated with various psychiatric syndromes include antiepileptic agents, antiparkinsonian drugs, medications with high anticholinergic properties, immunosuppressants, and immunomodulators. The essential mandate should be to consider the possibility of the drug-induced psychiatric syndrome until and unless proved otherwise. A good history taking, focusing specifically on assessing the temporal relationship between the use of medications and onset of psychiatric symptoms and understanding the relationship of change in medication doses with the onset of symptoms or increase in a decrease in symptoms, can be useful in identifying the drug-induced disorders. However, it is also important to remember that many a time, the drug-induced symptoms can emerge late during the therapy. This understanding often improves the diagnosis and helps to decide when to use psychotropics and how long.[19]
Have an Understanding of Drug Interactions
Drug interactions are a rule rather than an exception when using more than one drug. These can occur at the pharmacokinetic level or pharmacodynamic level. The pharmacokinetic interactions usually involve interaction at the level of plasma protein binding (displacement of a highly bound drug can lead to toxicity) and CYP450 enzyme level. The pharmacodynamic interactions will emerge when the patient is prescribed medications that may act on dopaminergic, serotonergic, or anticholinergic receptors. Different kinds of drug interactions can lead to toxicity or reduction in the efficacy of the prescribed psychotropics. Whenever in doubt, the clinicians can use available online calculators to evaluate interactions between different medications. Understanding drug interactions can help select new medicines or stop the offending agent in case the patient is experiencing toxicity or lack of efficacy.
Have Knowledge about Repurposing of Medications
The term “repurposing” literally means using the drugs for a new purpose or using medication for purposes other than already approved. Many psychotropics have been found in animal model studies to have antimalignancy properties, anti-infective properties, and anti-inflammatory properties [Table 3].[20],[21],[22] On the other hand, medications from different classes have been repurposed to manage psychiatric symptoms. For example, minocycline and doxycycline have been used for the management of negative and cognitive symptoms of schizophrenia.[23],[24] This understanding can help select various agents in persons with comorbid physical illnesses. The usefulness of medications of one class in a condition other than already can help reduce the total medication load, augment the partial response, and manage treatment resistance to conventional agents.{Table 3}
Conclusion
Psychiatrists need to remember that they are physicians and are responsible for screening their patients for various medical illnesses and facilitating effective management of the same. For this, they need to have a basic understanding of managing multiple physical diseases, especially metabolic disturbances. They need to work closely with other specialists rather than taking full responsibility for their patient's physical health at the hands of physicians. The psychiatrist should be well informed about basic facts about screening, monitoring, and managing various physical illnesses.
References
| 1 | Alegria M, Jackson JS, Kessler RC, Takeuchi D. National Comorbidity Survey Replication (NCS-R), 2001–2003. Ann Arbor: Interuniversity Consortium for Political and Social Research; 2003. |
| 2 | Piotrowski P, Gondek TM, Królicka-Deręgowska A, Misiak B, Adamowski T, Kiejna A. Causes of mortality in schizophrenia: An updated review of European studies. Psychiatr Danub 2017;29:108-20. |
| 3 | Grover S, Avasthi A, Sinha V, Lakdawala B, Bathla M, Sethi S, et al. Indian Psychiatric Society multicentric study: Prescription patterns of psychotropics in India. Indian J Psychiatry 2014;56:253-64. |
| 4 | Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: A systematic review and network meta-analysis. Lancet Psychiatry 2020;7:64-77. |
| 5 | American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27:596-601. |
| 6 | Sahoo S, Grover S. Hyponatremia and psychotropics. J Geriatr Ment Health 2016;3:108-22. |
| 7 | Rego T, Velakoulis D. Brain imaging in psychiatric disorders: Target or screen? BJPsych Open 2019;5:e4. |
| 8 | Lippmann S. Emergency brain imaging: CT or MRI? Curr Psychiatry 2013;12:55. |
| 9 | Thompson JL, Crossman RR. Drug-induced QT prolongation – A patient's risk of a fatal ventricular arrhythmia may be reduced if the pharmacist is aware of non-pharmacologic risk factors, drugs known to cause QT prolongation, and specific drug interactions. US Pharm 2007;32:44. |
| 10 | Pisani F, Oteri G, Costa C, Di Raimondo G, Di Perri R. Effects of psychotropic drugs on seizure threshold. Drug Saf 2002;25:91-110. |
| 11 | Handelsman Y, Jellinger PS, Guerin CK, Bloomgarden ZT, Brinton EA, Budoff MJ, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm – 2020 executive summary. Endocr Pract 2020;26:1196-224. |
| 12 | Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India 2009;57:163-70. |
| 13 | Fitzgerald I, O'Connell J, Keating D, Hynes C, McWilliams S, Crowley EK. Metformin in the management of antipsychotic-induced weight gain in adults with psychosis: Development of the first evidence-based guideline using GRADE methodology. Evid Based Ment Health 2022;25:15-22. |
| 14 | Liang H, Li H, Hu Y, Li S, Lü L, Song X. Effects of Topiramate for atypical antipsychotic-induced body weight gain and metabolic adversities: A systematic review and meta-analysis. Zhonghua Yi Xue Za Zhi 2016;96:216-23. |
| 15 | Shah SN, Munjal YP, Kamath SA, Wander GS, Mehta N, Mukherjee S, et al. Indian guidelines on hypertension-IV (2019). J Hum Hypertens 2020;34:745-58. |
| 16 | Whelton PK, Carey RM, Aronow WS, Casey DE Jr., Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018;71:1269-324. |
| 17 | Indian Council of Medical Research. ICMR Guidelines for Management of Type-2 Diabetes. New Delhi: Indian Council of Medical Research; 2018. |
| 18 | Grover S, Sarkar S, Avasthi A. Management of systemic medical emergencies associated with psychotropic medications. Indian J Psychiatry 2022;64:S252-80. |
| 19 | Niebrzydowska A, Grabowski J. Medication-induced psychotic disorder. A review of selected drugs side effects. Psychiatr Danub 2022;34:11-8. |
| 20 | Golden SR, Rosenstein DL, Belhorn T, Blatt J. Repurposing psychotropic agents for viral disorders: Beyond covid. Assay Drug Dev Technol 2021;19:373-85. |
| 21 | Vlachos N, Lampros M, Voulgaris S, Alexiou GA. Repurposing antipsychotics for cancer treatment. Biomedicines 2021;9:1785. |
| 22 | Huang J, Zhao D, Liu Z, Liu F. Repurposing psychiatric drugs as anti-cancer agents. Cancer Lett 2018;419:257-65. |
| 23 | Deakin B, Suckling J, Barnes TR, Byrne K, Chaudhry IB, Dazzan P, et al. The benefit of minocycline on negative symptoms of schizophrenia in patients with recent-onset psychosis (BeneMin): A randomised, double-blind, placebo-controlled trial. Lancet Psychiatry 2018;5:885-94. |
| 24 | Ben-Azu B, Omogbiya IA, Aderibigbe AO, Umukoro S, Ajayi AM, Iwalewa EO. Doxycycline prevents and reverses schizophrenic-like behaviors induced by ketamine in mice via modulation of oxidative, nitrergic and cholinergic pathways. Brain Res Bull 2018;139:114-24. |
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