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1. Case Conference Chairperson: Dr Debadatta Mohapatra (Associate Professor) Mentor: Dr Vandana Naik (SR) Presenter: Dr Zafar Mahmood (JR)

2. Sociodemographic Details Mr. JR/ 40 years/ Unmarried man/ Hindu Joint Family/ Lower Middle Socio-economic status/ 8 th /Daily wage worker(mason) / Khorda Odisha Informant details Mother living with him through out the illness Self Medical Records Information provided is reliable and adequate

3. TDI years 18 years Age of Onset- When he was 22 years old Mode of Onset : Insidious Course : Deteriorating

4. Chief complaints According to Patient I have no complaint According to Informant He is smoking cannabis since 20 years He is talking to himself since 18 years He is suspicious of everyone 18 years He is getting aggressive since 18 years

5. HOPI 18 years back Mr JR was 23 years old daily wage labourer(mason), In this period he used to work in field. He used to have active lifestyle and he used to get around 5-6 in morning, have his breakfast and go to work, he would work till 2 then have his lunch and finish his work by 5-6 then socialise with friends. Occasionally in 15-20 days he would take cannabis in form of chillum with his friends amount of cannabis used in that period is not known and also used to take 3-4 packets of gutkha and 2-3 beedis daily since last 4 years. As per mother he has been taking Cannabis for last 2 years before onset and details about initiation couldn’t be obtained

6. 18-17 years back He was maintaining like this till 18 years back when family members noticed that he is appearing lost in his own world most of time and would not be able answer correctly and give them odd replies not relevant to matter. Gradually over few weeks family members noticed he is becoming more irritable and getting aggressive towards minor matter like type of food prepared.

7. 18-17 years back There were few incidences as per mother when he got assaultive and threw things at family but mother doesn’t recollect cause of these incidents Family members also noticed that patient has become less social and not interacting with his peers at work. Over next 4-5 months they would notice that patient has become less responsive emotionally, would be withdrawn and would only get angry time to time

8. 17 years back In this period as per family members he would sometimes be seen smoking cannabis sometimes alone which was not like himself but they would see this occasionally once or twice a month. Over period of next 1 months family members noticed that he has started sitting alone most of the days and stopped going to work, they also noticed that he seems to be in animated conversation with someone but no one would be around him. Gradually his talking to himself increased and he would rarely speak to family members and sit and mutter to himself most of the time

9. 17 years back When family would question him about the same , he would get angry and occasionally hit his brother and mother. In this period he would stay awake till late at night and keep talking to himself while roaming aimlessly around in his home He would take his meals at times but would rarely take bath or take care of himself Seeing his increased aggression and poor self care family members on advise of villagers took him to a local doctor where he was prescribed some medications(details not available)

10. 16 years ago…. Mother reports that over next 6 months, patient would feel extremely sleepy but his aggression has come down significantly He would still take cannabis once or twice a months and beedi and gutkha in previous pattern As per mother his talking to himself has decreased but not completely gone but he has started going back to work Seeing his improved condition 15 years ago, his family member arranged his marriage on advice of relative and he was married at age of 26

11. 15-13 years ago In first year of marriage as per mother patient was maintaining relatively well with his medication being supervised by family members After one year couple had a girl child and in this period he would be aggressive occasionally at his wife and would be seen talking to himself occasionally After this family members thought, he doesn’t need medication stopped his medications around 13 years ago

12. 12 years ago… Gradually as per mother, he started smoking Ganja every day and would used to spend around 30-50 Rs every day on smoking cannabis Often he would return home with eye blood shot and a distinct smell of cannabis coming from his clothes, and he would often demand food on returning home and would get aggressive towards wife if he would not get the same immediately As per mother he started suspecting his wife of having affair with some one in village and would get angry when she would leave home.

13. 11 years back He would often follow his wife if she went outside of home and would beat her when she would come back, as per mother in those days he would talk as if he was sure that wife was cheating on him His talking to himself would further increased and he would occasionally disclose to his wife that he hears voices that some from some distance away in the village, these were 3-4 voices both male and female and they would talk nicely to him ask about his well being and he would like talking to them and sometimes he would say that voices are talking about him and commenting on what he is doing. But on other occasions he would deny ever hearing voices and beat her if she questioned him and would not disclose the content

14. 10 years back Seeing his increased aggression and cannabis use family member took him to nearby medical college where he was started on some medications details of which is mentioned in treatment history. After taking medication his aggression decreased but he would keep talking to himself most of the time of the days. He gradually stopped going to work and stay at home and keep to himself , he would occasionally take cannabis but would take gutka and beedi in his previous pattern

15. 8-4years back As per family members he was maintaining same in this period on medication with occasional anger outburst, he would keep to himself and rarely venture out of home He would usually neglect his self care and has to be forced for same His family members would take him regularly to his doctor for follow up and medication would be changed and would be supervised by family members He would sleep adequately for around 7-8 hours

16. 4years -till 2024( last admission) Since 4 years patient restarted taking cannabis few times a months, family members doesn’t know exact pattern of consumption but as per them as he didn’t have much money of his own, it is highly likely he was not taking regularly. Gradually over last 2 years family members noticed that he is not taking medication and occasionally spitting it out as this would be occasional they would not pay much attention In this period his talking to himself would persist and he would be not taking care of himself but his sleep would be 7-8 hours and he would take 3 timely meals

17. 6 month before admission his family members started to note that he has become more demanding of money especially to smoke cannabis which he was now taking around every 4-5 days and would get violent if he would not get same He has in these month stopped caring about himself and would often roam around in the village was often seen gesturing and talking to himself and he often become injured due to small stones thrown by local kids and villagers would complain to family members of his wandering behaviour

18. Last Admission Seeing deterioration in his condition he was brought to AIIMS Bhubaneswar and was admitted from 29/5/24 to 20/8/24 In this admission his risperidone was hiked up to 8 mg and he also received 10 sessions tDCS but as his aggression and talking to himself would persists and based on previous failed trail of Olanzapine up to 20mg and Amisulpride up to 600mg, tab Clozapine was started at 50mg a day and gradually hiked to 300 mg/day However at a dose of 300mg a day patient developed, pain abdomen and decreased urine out put and on investigation patient developed deranged kidney function and on advise of nephrology department clozapine as possible cause it was gradually tapered off in next 20 days with renal function monitoring and started on safer Haloperidol 5 mg a day.

19. He was diagnosed as Acute Kidney Injury/ Chronic tubulo-interstitial-nephritis after elevated creatinine, deranged UCR. And patient was discharged on request of family members 2 days after discharge his leg and hand would shake and gradually they would become rigid and his face would become mask like, gradually he would become slow and would have difficult to even go to bathroom seeing this he was brought to AIIMS Bhubaneswar and was admitted.

20. Negative History No history suggestive of thought being inserted/ taken out and broadcasted No history suggestive a firm fixed belief about him being controlled / or a bodily part being recipient of any sensation No history of bizarre firm fixed belief No history of any perceptual deception in other modality No history making same odd posture for long, resisting movement, waxy flexibility or other signs of catatonia

21. Negative History No history of not able to recognise family members/ tell time of the day/picking behaviour No history of history tremors, vivid images confusion No history of persistent low mood/ anhedonia/ worthless/ significant weight loss/ death wishes No history of persistent elevated mood/increased self esteem/ No history of repeated intrusive distressing thought images and impulses No history of any significant head injury/ seizure/ persistent fever and headache

22. Life Chart

23. Past History NIL SIGNIFICANT

24. Treatment History Medication Dose Range Duration Response Compliance Side Effects OLANZAPINE Upto 20mg 2018-2021 Poor Good Amisulpride Upto 600mg 2022-23 poor Good Risperidone Upto 8 mg 2024 for 2 months poor GOOD Clozapine Upto 300mg 1.5 months partial GOOD Hypersalivation, Constipation , Tachycardia, AKI

25. Ivabradine Upto 5 mg 1 month GooD good Haloperidol Upto 5 mg 8 days poor good Drug induced Parkinsonism tdCS 20 sessions poor poor

26. Family History 2 nd born of sibling Wife and mother are primary care givers History of Cannabis use in elder brother, pattern unknown Lost father 26 years back. Elder brother and wife are bread winners. Has 2 children No history any other known psychiatric disorder in Family members Mother has little knowledge about the nature of disease but she has been supervising his medication There is occasional critical comment from his older brother of him being burden on family

27. Pedigree

28. Personal History Birth and Developmental History: Nil significant Childhood and development History: Nil significant, Easy Child Educational History: Educated till class 8 th , Average Academically Occupational History: Worked as a mason in nearby villages , not working since last 8 years Sexual/Marital History Married 16 years back Other history couldn’t be obtained

29. Pre Morbid personality Social Relations: Used to be quite amicable and easily mixed, was mostly followers not usually taking lead but used to adjust to social situation Intellectual activities and Interest :He used to prefer group activity not much interest in intellectual activities as per mother Mood : Predominantly Euthymic Character Took responsibility after death of father, was known to be a responsible toward work

30. Not very religious or rigid as per mother Used to energetic before onset of illness Fantasy Life couldn’t be elicited Habits: Early riser, known to punctual to work

31. General physical examination Conscious, oriented to time, place and person PR: 94/min; BP: 100/70 mmHg; RR: 18/min; SpO2: 99% under RA Height: 164cm; Weight: 64kg, BMI:23.3 kg/m2 No Pallor/Icterus/ Cyanosis/ Clubbing/ Lymphadenopathy/ Edema Respiratory system - B/L Vesicular breath sounds heard no added sounds Cardiovascular system - S1,S2 heard, no added sounds Abdomen: Soft, Non tender , No organomegaly

32. Cranial Nerve Exam Cerebellar signs Unremarkable No signs of meningeal irritation

33. CNS EXAM

34. Mental Status Exam on 1/9/24 5PM Psychotherapy Room A middle aged man looking of stated age, well built, ill kempt in dishevelled clothes came to interview room with mother, patient didn’t seem to be in touch with surrounding and was mumbling and smiling while making occasional gestures. Patient was disinterested and seems not to care about interviewers questions was withdrawn and not paying any attention to interviewer Rapport couldn't be established

35. General reaction and posture Patient shows occasional gesturing and is untidy, eats voluntarily but need assistance in dressing, no slowness noted Patient is mostly apathetic towards examiner with occasional inappropriate smile and occasional in comprehensible muttering Take a comfortable posture and is shifting frequently

36. Facial movement and expression Facial expression are mostly mask like but having awkward smile occasionally Occasionally smiling

37. Eyes and pupils Eyes were open, occasionally gives attention to examiner Blinking is present

38. Reaction to examiners questions and tests Follows simple command like showing tongue and lifting hand No negativism – either active or passive No automatic obedience, echolalia and echopraxia

39. Muscular reactions No rigidity - lead pipe or cog wheel type, waxy flexibility, gagenhalten, mitgehen and mitmachen No urinary or faecal incontinence Emotional responsiveness : Emotional response blunted but occasional smiling when asked about family Startled and looks at examiner when hand is clapped

40. Speech: Spontaneous mostly irrelevant especially looking like in response to Hallucinations Writing: didn’t respond to aids given for writing

41. Diagnostic Formulation Index patient 40 years old Hindu married man belonging to Hindu joint family of Lower social status studied up to class 8 th worked as mason currently not working premorbidly well adjusted nil significant past personal family history presented to us with a total duration of illness 18 years insidious onset continuous course characterised by with Tabacco use since 23 years in dependence pattern last use 4 months ago currently on nicotine replacement, Cannabis use since 20 years in dependence currently abstinent since 5 months( tolerance, craving, salience, use despite harm) with fearfulness, muttering to self and hallucinatory behaviour and 2 nd person auditory hallucination, delusion of infidelity, aggression and anger outburst with poor self care, decreased interaction, with since last 5 days tremors, rigidity, generalised slowness with bio socio-occupational dysfunction with General physical exam unremarkable and mental status exam revealing uncooperative actively muttering male with irrelevant speech with poor judgement and insight

42. Diagnosis F29 Psychosis Not otherwise specified F17.22 Mental and Behavioural disorder due to Tabacco in dependence syndrome currently on replacement regime F12.21 Mental and Behavioural disorder due to cannabinoids in dependence syndrome current abstinent in protected environment Acute Kidney Injury\ Chronic Tubulonephritis Drug Induced Parkinsonism

43. Differential F20.0 Paranoid Schizophrenia (Treatment Resistant) F17.22 Mental and Behavioural disorder due to Tabacco in dependence syndrome currently on replacement regime F12.21 Mental and Behavioural disorder due to cannabinoids in dependence syndrome current abstinent in protected environment Acute Kidney Injury\ Chronic Tubulonephritis Drug Induced Parkisonism

44. Plan of Management Short term Admission under MHCA act Sec 89 in Psychiatry ward D2 To send CBC( with Absolute Neutrophil Count), Liver Function Test Renal Function Test, Fasting Lipid Profile, Random Blood sugar, To send for a Electro-cardiogram Scales PANSS, BPRS To further explore Psychopathology

45. Target Symptoms Tremors Rigidity Generalised slowness Muttering to self Poor self care Deranged Kidney Function

46. Management Haloperidol stopped and Phenergan 100 mg a day was started In view of drug induced parkinsonism PAC and Fundus examination was done for starting mECT in view of severity of symptoms for acute management. Nephrology consultation in view of elevated Serum creatinine, Albumin Creatinine ratio and deranged serum electrolyte Psychological Family members were counselled about nature of illness and reasons for motor symptoms Critical comments to be addressed Care giver burden to be addressed and supportive session for the same

47. Long term Plan to restart Clozapine after Nephrology review Clozapine monitoring to be restated Psychological Clozapine psychoeducation to be done again

48. Clozapine Induced AKI Estébanez C, et al[Acute interstitial nephritis caused by clozapine]. Nefrologia . 2002;22(3):277-81. Spanish. PMID: 12123128. Case Report A case of a 69 years old man developed acute renal failure due to interstitial nephritis during treatment with the drug clozapine, and that improve after to discontinuation of this drug. Davis EAK, Kelly DL. Clozapine-associated renal failure: A case report and literature review. Ment Health Clin. 2019 May 10;9(3):124-127 Case Report and Review A 53 /M was started on lithium and clozapine within 4 days of each other although lithium was discontinued after 7 days due to tremor. Routine labs showed an increase in serum creatinine, which was initially attributed to the recent lithium. However, the patient's kidney function continued to worsen, requiring discontinuation of clozapine despite a robust response to a low dose. Several years later, the patient's kidney function improved but has not returned to baseline Vantipalli P, Roy S, Koduri NM, et al. Acute Interstitial Nephritis Induced by Clozapine. J Med Cases. 2022 Case Report a 50-year-old male with treatment resistant schizoaffective disorder who developed clozapine-induced AIN, confirmed with kidney biopsy within 2 months of taking this medication. His kidney function improved with removal of the drug and treatment with steroids. However, his kidney function was again significantly impaired when rechallenged with even a lower dose of clozapine a year later. Kidney function returned to baseline after stopping clozapine.

49. A review by EAK Davis et al 2019 found fourteen cases of clozapine-associated renal failure or nephritis Doses of clozapine ranged from 25 to 700 mg/d with an average of 218.75 mg/d. Time to symptom onset ranged from less than 1 day to 3 months with an average of 20 days from clozapine initiation Fever was present in 11 cases, eosinophilia in 6, elevated C-reactive protein in 5 case and proteinuria in 10 cases. Six of the cases had renal biopsies performed that showed acute interstitial nephritis, and the others were diagnosed by other subjective and objective markers.

50. Clozapine was discontinued in all cases, and patients were treated with supportive therapy, steroids, antibiotics, and/or hemodialysis. Kidney function returned to baseline in 6 cases

51. Prescribing Anti psychotics In Renal Insufficiency No agent clearly preferred to another; however, avoid sulpiride and amisulpride avoid highly anticholinergic agents because they can contribute to urinary retention first generation antipsychotic – suggest haloperidol 2–6mg a day second generation antipsychotic – suggest olanzapine 5mg a day Monitor decline in renal function over a considerable period as a 30% change over two years is associated with a 5-fold increase in risk of ESRD. CKD progression is often non-linear Older adults (>65 years) should be assumed to have at least mild renal impairment, their serum creatinine may not be raised because they have a smaller muscle mass.

52. Estimate the excretory capacity of the kidney by calculating the glomerular filtration rate (GFR). Check proteinuria by measuring urinary albumin and calculate albumin/creatinine ratio. This is because proteinuria is a significant risk factor for progression to endstage renal disease

53. THANK YOU