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PSYCHOPHARMACOLOGY REVIEW

PSYCHOPHARMACOLOGY REVIEW

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PSYCHOPHARMACOLOGY REVIEW

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  1. PSYCHOPHARMACOLOGY REVIEW Dr. Jan Banasch

  2. Psychopharmacology Review • Anti-psychotics (including drugs to treat side effects) • Mood stabilisers • Antidepressants • Anxiolytics

  3. Objectives for Psychopharmacology Review • Distinguish the different classes of Anti-psychotics • Recognize side effect profiles of Anti-psychotics and their management • Distinguish between the choices of mood stabilizers • Recognize side effects of mood stabilizers and the pathophysiology of Lithium excretion • To be able to select an appropriate antidepressant based on patient and drug choice profiles • Distinguish the side effects of antidepressants and their efficacy for indicated syndromes • Understand the differences between short and long-acting benzodiazepines • Recognize the indication for benzodiazepines

  4. Anti-Psychotics Two major classes Conventional vs Atypical Atypical – 1st line Wide indications for use • Psychosis • Mood stabilizer • Anxiolytic • Sleep

  5. Atypical Anti-Psychotics – 1st line ONLY Risperidone comes in a long-acting depot injection

  6. Conventional Anti-psychotics

  7. DePot (Long acting injections) May be given weekly, Q 2-3-4 weeks Compliance Issues/Treatment under the M.H.A.

  8. Atypical Anti-Psychotic Side Effects • Weight gain • Metabolic syndrome • Prolactinaemia • Agranulocytosis • Akathisia • Extrapyramidal symptoms

  9. Weight Gain • Clozapine/Olanzapine/Quetiapine – worst offenders • No weight gain with Aripiprazole or Ziprasidone (in fact weight loss)

  10. Metabolic Syndrome • Weight gain, ↑BMI • Diabetes Type II – Metformin • Hyperlipidemia – Statins • Hypertension - antihypertensives

  11. Prolactinaemia • Risperidone only • Dose dependent (levels ↑ as dose ↑ ) • Treat: Parlodel (Bromocriptine) • Gynaecomastia, erectile dysfunction • Amenorrhea

  12. Agranulocytosis • Clozapine only • Neutropenia – “Hypersensitivity Reaction?” • Special blood protocol

  13. Extrapyramidal Symptoms • Including dystonia – most common with Ziprasidone and with high doses of any atypical • Overall less common than with conventional anti-psychotics

  14. Akathisia • Most common with Aripiprazole (Abilify) ie starting dose is too high • Can be seen with other atypicals, usually at higher doses

  15. Atypical Anti-psychotic Induced Movement Disorders • Clozapine – No incidence • Risperidone – Akathisia, dystonia, EPS rarely TD • Olanzapine – Akathisia, dystonia, EPS • Quetiapine – Akathisia, especially restless legs • Ziprasidone – high risk of Akathisia, EPS and dystonia • Aripiprazole – high risk of Akathisia – increase very slowly • Overall incidence is much lower than with conventionals • Dose dependent • Ethnic vulnerability

  16. Conventional Anti-Psychotic Side Effects • Extrapyramidal symptoms • Akathisia • Dystonia • Tardive dyskinesia • Neuroleptic malignant syndrome

  17. Extrapyramidal Symptoms • Bradykinesia, mask like face, pill rolling tremor, cogwheeling rigidity, drooling, shuffling gait – Parkinsonism • Treat: Benztropine/anti-cholinergic

  18. Akathisia • Internal restlessness, insomnia, suicidality • “Ants in Pants” feeling • Treat: • Propranolol • Benzodiazepines - Lorazepam • Requip (tardive akathisia) • Not responsive to Benztropine

  19. Dystonia • Oral Buccal: • Tongue enlargement (risk of asphyxia) • Lock jaw • Torticollis – twisted neck • Occulogyric Crisis - “white of eyes” • Epistotonus – back arching • Treat: Urgently - IV/IM Benzotropine – fast resolution/reversible • Early warning sign of high risk to develop T.D.

  20. Tardive Dyskinesia • Oral Buccal – lip smacking, pouting, tongue protruding, bon-bon sign • Truncal – includes respiratory dyskinesia, diaphragmatic (belching, odd guttural utterances) • Can be extensive – choreiform movements of limbs/trunk • Very disabling – irreversible • Treat: Switch to Clozapine, antispasmodics, high dose Vit E

  21. Neuroleptic Malignant Syndrome (N.M.S.) • Clinical Features: • High fever > 40o C • Labile vital signs • Tachycardia • Muscle rigidity • Elevated creatinine kinase > 1,000 • Delirium • Incontinence • Treat: • Conservatively & symptomatically but IN hospital • Could use Dantrolene (as in malignant hyperthermia) • D/C all meds • Complications: • Renal Failure • Death

  22. Common Agents to Treat E.P.S.

  23. Common Agents to Treat Akathisia

  24. A Case of Worsening Psychosis or is it? • A patient presents to the Emergency Room in a state of mental disorganization. They have a history of schizophrenia. They are receiving anti-psychotic medications. • What is the differential diagnosis?

  25. Worsening Psychosis ?Non-compliance New medication Under medicated • Akathisia Restlessness→insomnia→worsening of psychotic symptoms 2° to irritability • Anticholinergic Delirium Took too many Cogentin either to treat side effects or to get ‘high’ 4.Neuroleptic Malignant Syndrome

  26. Mood Stabilizers • lst Line • Lithium Carbonate 300-1800 mg • Valproic Acid • Sodium Valproate (Epival) 500-2000 mg • Carbamazepine (Tegretol) 400-1200 mg • 2nd Line • Gabapentin (Neurontin) 300-1800 mg • Lamotrigine (Lamictal) 200 mg • Topiramate (Topamax) 100-200 mg Anti-Convulsant medications

  27. Mood Stabilizers • Atypical Anti-Psychotic • Have mood stabilizing properties • Monotherapy • Combined with mood stabilizer • Includes: • Clozapine Aripiprazole • Quetiapine Ziprasidone • Olanzapine Risperidone (consta im depot & oral) • Conventional Anti-Psychotics – as mood stabilizers • Clopixol LA depot im • Fluanxol depot im aids compliance

  28. Mood Stabilizers • Lithium Carbonate • Gold Standard since 1942 • Efficacy in acute mania of Bipolar 1 • Up to 80% full or partial responder • Up to 80% prevention of future episodes • Lessens intensity, severity, frequency of future episodes • Tolerability is variable • Dose range – 600-1500 mg/day (single dose qhs) • Abrupt cessation precipitates mania in 50% • Therapeutic range – 0.5-1.5 serum level • Decreases suicide rate significantly

  29. Side Effects of Lithium • Hypothyroidism (5-15%) • Gastric upset (20%) • Weight gain – water retention (30%) • Acne/psoriasis worsens • Leucocytosis • Renal Failure (↓GFR ↑Creat) – tubulointerstitial nephropathy • Cognitive dulling (↓memory, distractible) • Fatigue • Mild tremor • ECG – nonspecific (reversible) T wave changes (20-30%) • Nephrogenic diabetes insipidus (↓renal ability to concentrate urine)

  30. Predictors of Lithium Carbonate Failure • Non-compliance • Rapid cycling • Mixed states • Dysphoric mania • Substance abuse

  31. Serum Levels for Lithium Precipitants: Dehydration NSAIDS/Ibuprofen Sodium depleting diuretics (thiazides) Check levels 7 days after desired dose achieved 12 hrs after last dose

  32. Symptoms of Toxicity • Diarrhea Dysarthria • Tremor (coarse) Confusion • Abdominal pain Seizures • Ataxia Coma • Vomiting Death • Hold Lithium dose until symptoms abate • Drink fluids/restore hydration • Check levels serially • Hemodialysis (severe)

  33. Valproate/Valproic Acid • Effective for pure and mixed mania • Rapid cycling • Equal in efficacy to Lithium (80-90%) • Therapeutic level – 350-700 • Dose range – 1000-1500 mg/day

  34. Valproate Side Effects • Hair loss • Weight gain • Neurocognitive effects • Polycystic ovary disease • GERD/Reflux

  35. Carbamazepine • Effective in pure and mixed mania (70%) • Not very effective for rapid cycling • Hepatic enzyme induction • ADRS: Rash/Agranulocytosis • Therapeutic level =17-50 • Dose range – 600-1200 mg/day

  36. Teratogenesis of Mood Stabilizers • Lithium: • 1st Trimester – Ebsteins anomaly of heart (1 in 1-2000 vs 1 in 20,000) • Restart at 20/40 • No breast feeding • Anti-convulsants: • (Valproate, Carbamazepine, Gabapentin, Lamotrigine, Topiramate) • Neural tube defects

  37. Antidepressants • SSRIs: Selective Serotonergic Reuptake Inhibitors • SNRIs: Selective NorepinephrineReuptake Inhibitors • “Others” RIMA: Reuptake Inhibitor of Monamine • TCA: Tricyclic Antidepressants • MAOI: Monamine Oxidase 1st Line 2ND Line

  38. SSRIs CATIE Study – Zoloft and Celexa ranked most effective of all antidepressants (head:head trials)

  39. SSRIs – Side Effects • Sexual Dysfunction: Cialis/Viagra • anorgasmia • erectile dysfunction • ↓ libido • Weight Changes Switch A/D • Prozac – loss • Paxil – large gain • GI Upset Settles with time and dose related • nausea • diarrhea • Serotonergic Syndrome Stop A/D • much like akathisia Benzodiazepines • hyperstimulation Propanolol • jitteriness • agitation • “ants in your pants” • NOT SAFE TO USE IN BIPOLAR DEPRESSION

  40. SNRI • Selective Norepinephrine reuptake inhibitor • Dual Action 5HT/NE • Venlafaxine (Effexor/EffexorXR) 75-350 mg Depression/Anxiety • Duloxetine (Cymbalta) 40-60 mg Depression/Anxiety • Side Effects: Venlafaxine: • - sexual dysfunction (5HT) • - severe withdrawal syndrome (flu like) very gradual tapering, no abrupt discontinuation • Cymbalta: • - dry mouth, constipation, insomnia give in AM • NOT RECOMMENDED FOR USE IN BIPOLAR DEPRESSION (triggers mania)

  41. “Others”

  42. TCA (Also have muscarinic, histaminic and alpha adrenergic effects)

  43. TCA Side Effects • Anticholinergic: - dry mouth - constipation - blurred vision Do not use in BPH or glaucoma Cardiotoxic – fatal in O/D Seizure - ↓threshold Safer to use in Bipolar Depression

  44. MAOIs & RIMA • Inhibitors of Monoamine Oxidase – A (acts on 5HT and N/E, DA and Tyramine) • Phenelzine (Nardil) 15-90 mg • Tranylcypromine (Parnate) 20-90 mg • Isocarboxazid (Marplan) 10-50 mg • RIMA Reuptake inhibitor of monoamine oxidase - B (phenylethylamine/DA) • Moclobemide (Manerix) 150-600 mg • Indicated for Anxiety Disorders, Bipolar Depression Atypical/masked Depression/SADS Anxiety D/O Bulimia

  45. MAOI Side Effects • Hypertensive Crisis – triggered by diet • MAOI diet: • Low Tyramine – (avoid cheeses, processed meat, red wine, chocolate) • OTC, cough/cold preparations • Stimulants, sympathomimetics, meperidine • SSRIs, Wellbutrin, Remeron, SNRIs Leads to severe headache/hypertension with risk of death or stroke • Treat: IV Phentolamine • Patients must warn surgeons/dentists if having procedures • Need a two week wash-out period

  46. MAOI • May cause agitation, euphoria • May cause hypotension • Not safe to use in Bipolar Depression • RIMA – side effects • No need for low Tyramine diet • Safer to use in Bipolar Depression

  47. Anxiolytics • Indications: • Short term use • Treatment of generalized Anxiety Disorder • Adjunct treatment with antidepressants to cover the period before antidepressant becomes therapeutic • Akathisia • Hypnotic (short term, acute situations) • Alcohol withdrawal syndromes • Risks: • Addictive • Cognitive impairment • Disinhibition (Borderline Person D/o, Dementia) • Do not use in patients with sleep apnea (respiratory depression) • O/D risk when taken alone is low

  48. Benzodiazepines Commonly used as Anxiolytics

  49. Pharmacokinetics of Benzodiazepines • Rapidly absorbed from GI Tract • Poorly absorbed im (except Lorazepam) • Hepatic oxidation metabolic pathway (long acting) • Short acting benzodiazepines are metabolized by glucuronide conjugation – have no active metabolites • Short acting BZP – Lipophilic (rapid transfer across blood-brain barrier) • Long acting – subject to “build up” especially in elderly