ADVERSE EFFECTS OF ANTIPSYCHOTICS part 2.pptx

adverse effects of psychotropics

1. ADVERSE EFFECTS OF ANTI PSYCHOTICS RX [APT] DR.GAYATRI DEVI CHERUKURI 1 ST YEAR RESIDENT MODERATOR: DR.L.SRIKANTH ASSISTANT PROFESSOR DR.PSIMS&RF .

2. OBJECTIVES INTRODUCTION EXTRAPYRAMIDAL SYMPTOMS NEUROLEPTIC MALIGNANT SYNDROME ECG CHANGES WEIGHT GAIN PLASMA LIPIDS DIABETES BP CHANGES HYPONATREMIA SEXUALDYSFUNCTION HYPERPROLACTINEMIA PNEUMONIA VENOUS THROMBOEMBOLISM ADVERSE EFFECTS OF CLOZAPINE PREGNANCY

3. INTRODUCTION Antipsychotic medications [ NEUROLEPTICS , MAJOR TRANQUILIZERS ] are used to treat symptoms of psychosis , like hallucinations , delusions , paranoia. Like most other medications ,antipsychotics have certain side effects . Benefits are obscured by their adverse effects . Side effects range from minor tolerability issues [mild sedation , dry mouth] to unpleasant [constipation, akathisia, sexual dysfunction]to painful [acute dystonia ] to disfiguring [weight gain , tardive dyskinesia] to life threatening [myocarditis, agranulocytosis]. 1 st generation antipsychotics 2 nd generation antipsychotics Mostly of movement [EPS ] side effects Mostly of metabolic side effects .

4. EPS NIGROSTRIATAL PATH DYSTONIA[MUSCULAR SPASM] AKATHISIA [INNER RESTLESSNESS] PSEUDOPARKINSONISM [ bradykinesia ,tremors etc; ] TARDIVE DYSKINESIA [ABNORMAL INVOLUNTARY MOVEMENTS ] TIME TO DEVELOP WITHIN HOURS HOURS TO WEEK DAYS TO WEEKS MONTHS TO YEARS SIGNS AND SYMPTOMS Muscle spasm in any part of the body, e.g. Eyes rolling upwards (oculogyric spasm) Head and neck twisted to the side (torticollis) A subjectively unpleasant state of inner restlessness with a desire or compulsion to move Foot stamping when seated Constantly crossing/uncrossing legs Rocking from foot to foot Constantly pacing up and down Tremor and/or rigidity Bradykinesia (decreased facial expression, flat monotone voice, slow body movements, inability to initiate movement) Bradyphrenia (slowed thinking) Salivation Lip smacking or chewing Tongue protrusion (‘fly catching’) Choreiform hand movements (‘piano playing’) Dystonic and choreoathetoid movements of the limbs

5. AKATHISIA TARDIVE DYSKINESIA

6. DYSTONIA AKATHISIA PSEUDOPARKINSONISM TARDIVE DYSKINESIA SCALES BARNES AKATHISIA RATING SCALE SIMPSON ANGUS EPS SCALE Abnormal Involuntary Movement Scale (AIMS) RX ANTICHOLINERGICS ( ORAL, IV[ response in 5 mins ],IM ) ECT BOTULINUM TOXIN Reduce dose Change to lower propensity drug low-dose propranolol, 30–80mg/day, clonazepam (low dose), 5HT2 antagonists cyproheptadine, mirtazapine, trazodone, mianserin , and cyproheptadine Diphenhydramine. Reduce dose Change to lower propensity drug. ANTICHOLINERGIC [ reviewed at least every 3 months.] Stop anticholinergic Reduce dose Change to lower propensity drug , Clozapine Quetiapine valbenazine , deutetrabenazine & Tetrabenazine . VITAMIN E

7. NEUROLEPTIC MALIGNANT SYNDROME [NMS] NMS is an acute disorder of thermoregulation and neuromotor control. Characterized by muscular rigidity, hyperthermia, altered consciousness, and autonomic dysfunction, following exposure to antipsychotic medication Elevated creatine kinase ,leukocytosis , altered LFT’s. Risk factors : male, dehydration, exhaustion and confusion/agitation. High-potency FGAs seem to have the highest incidence, while SGAs and low potency FGAs have lower incidences.

8. TREATMENT RESTARTING ANTISYCHOTICS Psychiatric unit : withdraw antipsychotics monitor vitals I.M LORAZEPAM [BZD’S ] Medical unit : Rehydration bromocriptine+ dantrolene sedation with BZD’S Artificial ventilation if req L-dopa, apomorphine, carbamazepine ECT Stop antipsychotics for 5 days [allow NMS to resolve completely ] Begin very small dose and increase slowly Monitor vitals Aripiprazole , quetiapine ,clozapine . Avoid depot/ LAI and high potency FGA’S.

9. ECG CHANGES—QT PROLONGATION Antipsychotics block cardiac potassium channels and are linked to prolongation of the cardiac QT interval, a risk factor for the ventricular arrhythmia, torsade de pointes, which is fatal. OTHER ECG CHANGES: Atrial fibrillation, giant P waves ,T waves , Heart block. Perform ECG at the time of admission and if prior abnormality or additional risk factors present –yearly check up is done .

10. High effect Moderate effect Low effect No effect Unknown effect Any intravenous antipsychotic Pimozide Sertindole High doses of drugs . Amisulpride Chlorpromazine Haloperidol Iloperidone Levomepromazine Melperone Pimavanserin Quetiapine Ziprasidone Aripiprazole Asenapine Clozapine Flupentixol Fluphenazine Perphenazine Prochlorperazine Olanzapine Paliperidone Risperidone Sulpiride Brexpiprazole Cariprazine Lurasidone Lumateperone Loxapine Pipotiazine Trifluoperazine Zuclopenthixol

11. METABOLIC SYNDROME Major side effect of the atypical antipsychotics mostly with clozapine , olanzapine .

12. WEIGHT GAIN – Histamine receptor Mechanisms : 5HT2C antagonism, H1 antagonism, D2 antagonism, and increased serum leptin (leading to leptin de sensitization ). Weight gain is more in antipsychotic-naïve patients and during early stages of treatment of psychotic illness , women are at greater risk than men. HIGH MODERATE LOW Clozapine Olanzapine Chlorpromazine Iloperidone Sertindole Quetiapine Risperidone Paliperidone Amisulpride , Asenapine Brexpiprazole , Aripiprazole Cariprazine , Haloperidol Lumateperone Lurasidone , Sulpiride Trifluoperazine Ziprasidone

13. NON PHARMACOLOGICAL MANAGEMENT Weight gain has consequences on self-image, morbidity and mortality. Prevention and RX are matters of clinical urgency. Body mass index (BMI) and waist circumference should be recorded. Early in Rx, monitoring of body weight every week , for first 6 months . With continuing antipsychotic treatment , annual measurement of body weight is recommended as a minimum.

14. PHARMACOLOGICAL MANAGEMENT Stopping APT . Switching [ aripiprazole, ziprasidone lurasidone ]and augmentation strategies may minimise further weight gain . Additional lifestyle interventions required if BMI should be in normal range. Pharmacological methods [ Amantadine, liraglutide , metformin , topiramate , zonisamide ] should be considered only if non pharmacological RX is not useful. Metformin is DOC for the prevention and RX of APT-induced weight gain. GLP-1 agonists prove more effective and better tolerated. Bariatric surgery have role in few .

15. EFFECT OF APT ON PLASMA LIPIDS DYSLIPIDEMIA is an established risk factor for cardiovascular disease which may lead to morbidity and mortality. FGAs, phenothiazines associated with increases in triglycerides and LDL cholesterol and decreases in HDL cholesterol. SGA’S profound effect on triglycerides.

16. Other antipsychotic medications Fasting lipids at baseline, 3 months, and then annually Clozapine Olanzapine Fasting lipids at baseline then every 3 months for a year, then annually

17. TREATMENT Patients with raised cholesterol benefit from dietary advice, lifestyle changes and/or RX with statins. If triglycerides alone raised, diets low in saturated fats, and taking of fish oil and fibrates are effective treatments. Moderate to severe hyperlipidaemia develops during antipsychotic treatment, a switch to another antipsychotic medication . Aripiprazole and other D2 partial agonists : TOC in those with prior antipsychotic-induced dyslipidaemia Metformin added to antipsychotic medication may improve total cholesterol and triglyceride levels

18. DIABETES AND IMPAIRED GLUCOSE TOLERANCE Mechanisms : 5HT2A/5HT2C antagonism, Increased plasma lipids, weight gain and leptin resistance. Insulin resistance may occur in the absence of weight gain. FGA’S : Phenothiazine derivatives > fluphenazine or haloperidol, loxapine associated with impaired glucose tolerance and diabetes SGA’S: Clozapine ,OLANZAPINE > RISPERIDONE , QUETIAPINE is strongly linked to hyperglycaemia , impaired glucose tolerance and DKA.

19. HIGH RISK MODERATE RISK LOW RISK MINIMAL RISK [USED IN RX] Clozapine olanzapine Quetiapine, Risperidone, Phenothiazines High-potency FGAs (e.g. Haloperidol) Aripiprazole, Amisulpride , Asenapine , Brexpiprazole , Cariprazine , Lumateperone , Lurasidone, Ziprasidone

20. RX: Aripiprazole , Amisulpride , Asenapine , Brexpiprazole , Cariprazine , Lumateperone , Lurasidone, Ziprasidone;GLP-1 agonists.

21. ORTHOSTATIC HYPOTENSION (POSTURAL HYPOTENSION)- RISK FACTORS RISK FACTORS RISK FACTORS SYMPTOMS DRUGS: Antipsychotics with a high affinity for postsynaptic α1-adrenergic receptors are most frequently implicated. Clozapine quetiapine iloperidone lurasidone asenapine PATIENT FACTORS : Old age Disease with autonomic dysfunction (e.g. Parkinson’s disease) Dehydration Cardiovascular disease TREATMENT FACTORS: Intramuscular administration route Rapid dose increases Antipsychotic polypharmacy Drug interactions (e.g. β- blockers and other antihypertives } dizziness, light-headedness, asthenia, headache, and visual disturbance result in syncope and falls-related injuries. It also been associated with an increased risk of coronary heart disease, heart failure and death. Block

22. MONITOR NONPHARMACOLOGICAL THERAPIES PHARMACOLOGICAL TREATMENT Limit initial doses and titrate slowly. Temporary dose reduction Avoid drugs that are potent α1 antagonists smaller and more frequent dosing. Advice to patients, e.g. sitting on the edge of the bed for several minutes before attempting to stand in the morning and slowly rising from a seated position, may be helpful Abdominal binders and compression stockings. Increasing fluid intake to 1.25–2.5 l/day is advisable for all patients who are not fluid restricted. Sodium chloride Fludrocortisone Midodrine (an α1 receptor agonist)

23. HYPERTENSION Slow steady rise in blood pressure over time. Unpredictable rapid sharp increase in blood pressure on starting a new drug or increasing the dose Linked to weight gain. Being overweight increases the risk of developing hypertension Increases in blood pressure occur shortly after starting, ranging from within hours of the first dose to a month. RISK CAUSING TREATMENT CLOZAPINE ,OLANZAPINE RISPERIDONE,ARIPIPRAZOLE SULPRIDE,QUETIAPINE ZIPRASIDONE PERPHENAZINE Switch the drug VALSARTAN TELMISARTAN

24. HYPONATRAEMIA IN PSYCHOSIS WATER INTOXICATION : water consumption exceeds maximal renal clearance capacity. Serum and urine osmolality are low. Hyponatremia secondary to fluid overload. SIADH: kidney retains excess solute free water.(serum osmolality low ; urine osmolality relatively high) Fluid restriction with careful monitoring of serum Sodium. Consider treatment with clozapine Demeclocyclin e used for psychogenic polydipsia. Reducing/increasing dose of an antipsychotic will not result in improvements in serum sodium in water-intoxicated patients. If mild, fluid restriction with careful monitoring of serum sodium. Refer urgently to specialist medical care if Na < 125mmol/L. Switching to a different antipsychotic drug. Demeclocycline Lithium is effective but a potentially toxic drug – hyponatraemia predisposes to lithium toxicity

25. Tolvaptan , a so-called vaptan (non-peptide arginine-vasopressin antagonist – also known as aquaretics because they induce a highly hypotonic diuresis) , hyponatremia due to drug-related SIADH and psychogenic polydipsia . Successful use of the carbonic anhydrase inhibitor acetazolamide . Irbesartan, propranolol , Clonidine, enalapril and captopril have also been used in psychogenic polydipsia.

26. SEXUAL DYSFUNCTION In human sexual response 4 phases: 1.Desire Based on testosterone levels in men Increased by dopamine and decreased by prolactin 2.Arousal Influenced by testosterone in men and oestrogen in women Mechanisms : central d opamine stimulation, modulation of the cholinergic/adrenergic balance, peripheral α1 agonism and NO pathways. 3.orgasm Related to oxytocin Inhibition by increase in serotonin activity and raised p rolactin , as well as α1 blockade 4.Resolution Occurs passively after orgasm

27. RISKS: CLOZAPINE α1 adrenergic blockade and anticholinergic effects. No effect on prolactin Probably fewer problems than with typical antipsychotics. RISPERIDONE Potent elevator of serum prolactin; Less anticholinergic than some other antipsychotics (olanzapine, quetiapine); peripheral α1 adrenergic blockade leads to ejaculatory problems [retrograde] Priapism rare .Prevalence of sexual dysfunction reported to be 60–70% Thioxanthenes (e.g. flupentixol) Arousal problems and anorgasmia HALOPERIDOL Similar problems to the phenothiazines but anticholinergic effects reduced Prevalence of sexual dysfunction reported to be up to 70% OLANZAPINE less sexual dysfunction than haloperidol due to relative lack of prolactin-related effects Priapism rare..Prevalence of sexual dysfunction reported to be >50%47 PALIPERIDONE Similar prolactin elevations to risperidone PHENOTHIAZINES (e.g. chlorpromazine) Hyperprolactinaemia and anticholinergic effects. delayed orgasm at lower doses followed by normal orgasm but without ejaculation at higher doses. Priapism has been reported with thioridazine, risperidone and chlorpromazine ( α1 blockade)

28. Men complain of reduced desire, inability to achieve erection , premature ejaculation, wome n complain about reduced enjoyment. peripheral α1 receptors antagonists and cholinergic receptors antagonists can cause priapism. Antipsychotic-induced sedation and weight gain may reduce sexual desire . TREATMENT: OTHERS SEROTONIN CHOLINERGIC/ ADRENERGIC PDE I ‘S DOPAMINE AGONIST Switch the drug Add aripirazole R/O organic causes ALPROSTADIL [PG’S] BREMELANOTIDE [MELANOCORTIN RECEPTOR AGONIST] BUSPIRONE [5HT1a PA] CYPROHEPTADINE [5HT2 antagonist] FLIBANSERIN [5HT1A A +5HT2A ANTAGONST +DA ANTAGONIST] P IMVANSERIN [INVERSE AGONIST 5HT 2A,2C ] BETHANECHOL [ACH] BUPROPION [NDRI] YOHIMBINE [ ALPHA 2 ANTAGONIST] Sildenafil tadalafil, lodenafil , vardenafil AMANTIDINE BROMOCRIPTINE

29. HYPERPROLACTINAEMIA – Tuberoinfundibular path Prolactin-elevating (high risk; major changes) Prolactin–elevating (low risk minor changes only) Prolactin-sparing (prolactin increase very rare) Risperidone Paliperidone amisulpride sulpride FGA’S Lurasidone Olanzapine paliperidone Aripiprazole Asenapine Brexpiprazole Cariprazine Clozapine Iloperidone Lumateperone Pimavanserin Quetiapine

30. OTHER RISKS SYMPTOMS TREATMENT stress, pregnancy and lactation, seizures, renal impairment and Prolactinoma. sexual dysfunction , menstrual disturbances, breast growth, Galactorrhea , Include delusions of pregnancy. Risk of osteoporosis ,breast cancer. First choice : Aripiprazole 5mg a day Second choice : DA agonists – cabergoline, bromocriptine, amantadine Metformin 2.5–3g a day

31. NORMAL LEVELS : 0-25 ng/ml ELEVATED : 25-118ng/ml HIGHLY ELEVATED : > 118ng/ml MONITOR : EVERY 3 MONTHS IF LEVELS INCREASED SYMPTOMATIC : SWITCH ANTIPSYCHOTICS AND ADD ARIPIPRAZOLE ASYMPTOMATIC : ADD ARIPIPRAZOLE ADJUNCTIVE RX: METFORMIN

32. PNEUMONIA RISK MECHANISM MONITOR Increase with clozapine olanzapine, multiple antipsychotics haloperidol risk increase with alzheimers disease lithium is protective sedation , dystonia or dyskinesia, dry mouth increasing the risk of aspiration general poor physical health or perhaps some ill-defined effect on immune response. Assume all antipsychotics increase the risk of pneumonia. Monitor all patients for signs of chest infection and treat promptly.

33. VENOUS THROMBOEMBOLISM RISK MECHANISM OUTCOME MONITOR Increased with low potency phenothiazines, prochlorperazine decrased risk with age Sedation* Obesity* Hyperprolactinaemia* Elevated phospholipid antibodies Elevated platelet aggregation** Elevated plasma homocysteine pulmonary embolism, Stroke myocardial infarction. Monitor closely all patients for signs of venous TE . Calf pain or swelling Sudden breathing difficulties Signs of myocardial infarction (chest pain, nausea, etc.) Signs of stroke (sudden unilateral weakness, etc.) Use the lowest therapeutic dose Encourage good hydration and physical mobility

34. CLOZAPINE –COMMON SIDE EFFECTS FIRST 4 WEEKS FIRST 6 WEEKS FIRST FEW MONTHS FIRST 4 MONTHS ANY TIME OTHERS HYPOTENSION [ fluid intake , moclobemide,desmopressin , fludrocortisone] HYPERTENSION TACHYCARDIA[ Bisoprolol,atenolol ] with fever ?myocarditis FEVER[ PCM] 1.NAUSEA[ ondansetron ] SEDATION[ SMALL DOSE] HYPERSALIVATION [ HYOSCINE 300 mcg] CONSTIPATION [ screen regularly, adequate fibre, fluid,exercise ; laxatives] 1.SEIZURES [ reducedose , topiramate, lamotrigine, gabapentin ] 2.NOCTURNAL- ENURESIS [ reduce dose,night time toilet training,desmopressin ] 3.GERD [ PPI’S ] 1. WEIGHT GAIN[ FISRT YEARS] 2. PNEUMONIA[ EARLY IN RX] 3. MYOCLONUS [ DURING DOSE TITRATION/ INCREASE PLASMA LEVELS]

35. CLOZAPINE – UNCOMMON SIDE EFFECTS ANY TIME FIRST WEEKS FIRST FEW MONTHS FIRST 3 MONTHS FIRST FEW WEEKS TO MONTHS BUT ANY TIME DELIRIUM HEART STROKE HYPOTHERMIA OCULAR EFFECTS STUTTERING SKIN REACTION THROMBOEMBOLISM PERICARDITIS AND PERICARDIAL EFFUSION EOSINOPHILIA HEPATIC FAILURE THROMBO-CYTOPENIA PANREATITIS [ FIRST 6 WEEKS ] PAROTID SWELLING [ FIRST FEW WEEKS ] COLITIS/G.I. NECROSIS[ 1 ST MONTH] AGRANULOCYTOSIS[ FIRST 3 MONTHS ] INTERSTITIAL LUNG DISEASE[ FIRST FEW MONTHS ]

36. AP’S ADVERSE EFFECTS ON ORGAN SYSTEMS HEAMATOLOGICAL : Temporary leukopenia ,agranulocytosis, purpura, hemolytic anemias, and pancytopenia . SKIN AND EYE EFFECTS : Allergic dermatitis and photosensitivity ,Urticarial, maculopapular, petechial, and edematous eruptions . Irreversible retinal pigmentation is associated with use of thioridazine. photosensitivity reaction [chlorpromazine] HEPATIC : Jaundice [Elevations of liver enzymes]. Overdose of antipsychotics : Lethargy, coma, tachycardia, hypotension, hypersalivation, pneumonia, seizures, Sedation, coma, dystonia, NMS, QT prolongation, arrhythmia.

37. PREGNANCY FGA’S : preterm birth , LBW , early somnolence, jitteriness, limb defects[ haloperidol ] ,Neonatal dyskinesia , Neonatal jaundice [phenothiazines]. SGA’S: I ncreased birth weight, cardiac septal defects , tetralogy of fallot , anorectal atresia/stenosis and gastroschisis. Olanzapine – LBW, risk of intensive care admission, macrosomia; gestational diabetes, hip dysplasia, meningocele, ankyloblepharon , neural tube defects . clozapine -gestational diabetes and neonatal seizures. BREAST FEEDING : clozapine should be continued if mother is using . Better avoid butryphenones , phenothiazines ,clozapine, olanzapine, risperidone

38. SIDE EFFECTS OF DEPOT PREPARATIONS Pain/swelling at injection site ,rarely abscesses , nerve palsies. More likely to cause EPS than oral preparations. POST INJECTION SYNDROME : Idiosyncratic excessive sedative akin to olanzapine overdose b/w 1-6 hrs post injection. After injection ,patient should be observed for atleast 3 hrs for any signs of this syndrome.[sedation ,confusion/aggression , EPS , dysarthria / ataxia ,seizure].

39. SUMMARY Antipsychotic medications [ NEUROLEPTICS , MAJOR TRANQUILIZERS ] are used to treat symptoms of psychosis , like hallucinations , delusions , paranoia. ACTION BY BLOCKING RECEPTORS EFFECTS DOPAMINE Mesolimbic – decrease positive symptoms ; mesocortical – worsen – ve symptoms ; Nigrostriatal – EPS; Tuberoinfundibular- decrease dopamine -> increase prolactin ->oligomenorrhea, galactorrhoea ,gynecomastia ; chemoreceptor trigger zone – decrease nausea , vomiting SEROTONIN Mesocortical – 5HT 2A ‘ R ‘ block –>increase dopamine  less –ve symptoms HISTAMINE Sedation , antipruritic action ,weight gain . MUSCARINIC Anticholinergic s/e – Dry mouth , blurred vision , urine retention , constipation ALPHA -1 Orthostatic hypotension ,dizziness , drowsiness

40. Low potency [ Chlorpromazine , thioridazine ] drugs cause more sedation but less EPS . Chlorpromazine – corneal deposits [ vortex keratopathy] Thioridazine – retinal deposits [ irreversible ] . Quetiapine – cataract . Clozapine [ seizures , agranulocytosis] , olanzapine –METABOLIC SYNDROME . Ziprasidone – prolong QT interval [ no weight gain] . Neuroleptic malignant syndrome . PREGNANCY : preterm birth , LBW , limb defects[ haloperidol ] ,Neonatal dyskinesia , Neonatal jaundice [phenothiazines], Increased birth weight, cardiac septal defects (co-exposure to SSRIs),tetralogy of fallot . DEPOT PREPARATIONS : Pain/swelling at injection site ,rarely abscesses , nerve palsies, EPS, POST INJECTION SYNDROME .

41. REFERENCES 1.Taylor D, Paton C, Kapur S. The Maudsley prescribing guidelines in psychiatry. 12th ed. Hoboken, NJ: Wiley-Blackwell; 2015. (5) 2.Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications [Internet]. Cambridge, England: Cambridge University Press; 2022. 3. Sadock BJ, Ahmad S, Sadock VA. Kaplan & sadock’s pocket handbook of clinical psychiatry. 6th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2018.

42. PHYSIOLOGICAL RISK FACTORS FOR QTC PROLONGATION AND ARRHYTHMIA CARDIAC METABOLIC OTHERS Long QT syndrome Bradycardia Ischaemic heart disease Myocarditis Myocardial infarction Left ventricular hypertrophy Hypokalaemia Hypomagnesaemia Hypocalcaemia Extreme physical exertion Stress or shock Anorexia nervosa Extremes of age – children and elderly may be more susceptible to QT changes Female gender

43. NON-PSYCHOTROPICS ASSOCIATED WITH QT PROLONGATION ANTIBIOTICS ANTIARRYTHMICS ANTIMALARIALS OTHERS Erythromycin Clarithromycin Ampicillin Co-trimoxazole Pentamidine Quinidine Disopyramide Procainamide Sotalol Amiodarone Bretylium Chloroquine Mefloquine Quinine Amantadine Cyclosporin Diphenhydramine Hydroxyzine Methadone Nicardipine Tamoxifen

44. CATATONIA RETARDED/STUPOROUS FORM EXCITED FORM mutism, rigidity, marked psychomotor retardation, negativism, posturing, waxy flexibility, and catalepsy. Agitation, combativeness, impulsivity and apparently purposeless overactivity. ASSOCIATED PSYCHIATRIC CONDITION : schizophrenia, depression , mania, alcohol or benzodiazepine withdrawal, conversion disorder. If psychiatric stupor is left untreated, lead to serious complications such as dehydration, venous thrombosis, pulmonary embolism, pneumonia, and ultimately death .

45. RX OTHER THAN BENZODIAZEPINES FOR CATATONIA/STUPOR ANTIPSYCHOTIC MEDICATIONS: EXPERIMENTAL TREATMENTS: ■ Aripiprazole ■ Clozapine ■ Olanzapine ■ Risperidone ■ Ziprasidone Amantadine ■ Amitriptyline ■ Carbamazepine ■ Fluoxetine ■ Fluvoxamine ■ Lithium ■ Memantine ■ Methylphenidate ■ Mirtazapine ■ Tramadol■ Valproate ■ Zolpidem.

46. PREGNANCY: No clear evidence that antipsychotic is major teratogen. Continue drug if previously responded to rather than switching prior to/during pregnancy. CYP 2D6 activity is increased , CYP 1A2 is reduced at the end of pregnancy . Screen for adverse metabolic effects &offer oral glucose tolerance test. Woman should give birth in a unit with access to neonatal ICU facilities. Quetiapine has relative low rate of placental passage. Reproductive safety data available for quetiapine, olanzapine, risperidone, haloperidol BREAST FEEDING : clozapine should be continued if mother is using . If initiating in postpartum olanzapine or quetiapine are considered. Better avoid butryphenones , phenothiazines ,clozapine, olanzapine, risperidone

47. SUMMARY Antipsychotic medications [ NEUROLEPTICS , MAJOR TRANQUILIZERS ] are used to treat symptoms of psychosis , like hallucinations , delusions , paranoia.