1 / 44

Drugs Used in Psychiatry

Drugs Used in Psychiatry. Dr Noel Kennedy Clinical Lecturer and Consultant Psychiatrist. Schizophrenia. Positive symptoms - delusions - hallucinations Negative symptoms - apathy - avolition. Schizophrenia – Diagnosis (Schneider, 1959). Hallucinations

latif
Download Presentation

Drugs Used in Psychiatry

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drugs Used in Psychiatry Dr Noel Kennedy Clinical Lecturer and Consultant Psychiatrist

  2. Schizophrenia • Positive symptoms - delusions - hallucinations • Negative symptoms - apathy - avolition

  3. Schizophrenia – Diagnosis (Schneider, 1959) • Hallucinations - third person - running commentary - thought echo • Thought interference or Somatic passivity • Delusional perception (also bizarre delusions DSM-IV, one month duration0

  4. Schizophrenia - Epidemiology • 1% prevalence, higher cities, ethnic minorities • M>F, late teens to early 20s • Two peaks in onset - early onset, male, developmental delay, drugs - late mid-life, female, preserved personality • Interst in substance abuse, prenatal viral exposure • Poor outcome - >80% relapse, majortiy impaired

  5. Schizophrenia Aetiology • Genetic - First degree relative 10% - Twin studies MZ:DZ 48:4, Adoption studies • Neurochemical - D2 blockade (amphetamines, animal models, receptor occupancy) - Serotonin blockade(?5HT2 block, LSD,.5HT impact on dopamine ) - Glutamate (NMDA antagonists e.g. ketamine)

  6. Antipsychotics- Classification

  7. Typical antipsychotics D2 Antagonism HPA (↑PRL) Mesolimbic (Antipsychotic) Basal Ganglia (EPSE, Parkinsonism)

  8. Typical Antipsychotics • High potency “Clean”(Likely EPSE) - Butyrophenones (e.g. haloperidol) - Piperazine (e.g. trifluoperazine) • Low potency “Dirty” (anticholinergic, antiadrenergic) - Aliphatic(e.g. chlorpromazine) - Thioxanthene (Zuclopenthixol)

  9. Extrapyramidal Side Effects • Acute Dystonia(Young men, early, first episode) • Parkinsonism (cog-wheeling, rigidity, bradykinesia) • Akathesia (uncontrollable restlessness, suicide risk) • Tardive Dyskinesia(long-term tx, female, elderly) • Neuroleptic Malignant Syndrome

  10. Neuroleptic Malignant Syndrome (NMS) • Early in tx (<4 weeks) M>F, 20% mortality,mid-life • Clinical - muscle rigidity - pyrexia - delirium - pyrexia - ↑↑CPK, ↑K ↓Neutorophils, Myoglobinurea • Treatment - respiratory support - bromocriptine/dantrolene

  11. Antipsychotics Other Side Effects • Anticholinergic (low potency) - blurred vision, constipation, confusion, wt gain • Antiadrenergic (low potency) - postural hypotension, sexual • ↓ Seizure threshold • Weight gain (low potency, clozapine, olanzapine) • Neutropenia/Agranulocytosis (clozapine) • Diabetes/Impaired GTT (clozapine, olanzapine) • Cholestatic jaundice (chlorpromazine) • ECG change, QT prolongation (low effect)

  12. Atypical Antipsychotics • Definitions - Less EPSE - Mesolimbic specific or 5HT2/D2 antagonism • Clinical Potency - As effective as typicals in positive symptoms - Some more effective (clozapine>olanzapine/sulpiride>rest Davis et al.) - May have more effect on negative symptoms

  13. Atypical Antipsychotics • Sulpiride/Amisulpiride - D2 blockade mesolimbic specific, ↑PRL antidepressant • Risperidone - 5HT2/D2 blockade, EPSE high doses, little sedation, wt gain • Olanzapine - 5HT2/D2 blockade, significant weight gain (9%), sedation • Quetiapine - D2/5HT2/ blockade, sedative, few other s/e, ?potency • Clozapine - treatment resistant scz, multiple receptors, agranulocytosis

  14. Clozapine • Most effective treatment for treatment resistant schizophrenia(30% 6 weeks, 70% 1 year kane et al, 1988) • Multiple receptor occupancy (D1, D2, D4, D5, 5HT2, 5HT3, adrenergic, muscarinic) • Many side effects including agranulocytosis (2-3%) • May lead to reduction in suicide

  15. Clozapine Important Side Effects • Neutropenia - Weekly blood monitoring (18 weeks), 2-4 weeks afterwards • Seizures - Mainly myoclonic, dose related, valproate • Myocarditis/Cardiomyopathy - 1 in 10,000-20,000 • Pulmonary embolism - 1 in 5,000, effect on antiphospholipid antibodies • Diabetes and weight gain - 1/3rd within 5 years of treatment

  16. Clozapine Other Side Effects • Sedation (early) • Hypersalivation (hyoscine) • Hypertension/hypotension • Tachycardia (early) • Constipation • Fever

  17. Antipsychotics and Diabetes • Especially clozapine and olanzapine (30-40% diabetes long-term) • Usually early in treatment • Needs regular monitoring (Baseline HBA1C, OGTT, then 3-6 monthly)

  18. Depression Treatment: Symptoms • At least two of (>2 weeks): - persistent low mood (DMV) - anhedonia - poor energy • At least two of: - sleep disturbance - appetite disturbance/weight loss - impaired libido - guilt & cognitions - poor concentration - futility feelings/suicidal ideation - social withdrawal

  19. Depression - Epidemiology • 6-9% prevalence, higher women (F:M 2:1) • Late 20s throughout life • Higher rates cities, low social class • Poor outcome – high levels of disability - 10% chronicity - 10% unnatural death - 70% long-term recurence - 50% of time symptomatic over 10 years

  20. Depression and subsyndromal symptoms over 10-year follow-up (Kennedy et al, 2004)

  21. Theories of Depression • Monoamine Theory - Deficits of monamines 5HT/Nad - Most antidepressants increase monoamines • Neuroendocrine (HPA axis) - Hypercortisolaemia/loss of circadian rthymn - Failure of DST (60%) - Failure to supress CRH

  22. Antidepressants Classes • Monoamine oxidase inhibitors (MAOI) - ↑stores Nad/5HT by inhibiting MAO-A • Tricyclic antidepressants (TCA) – inhibits 5HT/Nad neuronal reuptake • Selective serotonin reuptake inhibitor (SSRI) – inhibits 5HT neuronal reuptake • Others - venlafaxine - Nad/5HT reuptake/receptor inhibition - mirtazepine - alpha 2, 5HT2 receptor inhibition - reboxetine – Nad reuptake inhibitor

  23. Management of Depression: General Principles • Antidepressants only effective (70%) • Partial response a problem (40%) • Length of treatment important (4-8 weeks) • Not all antidepressants are equal (meta-analysis) • Consider symptoms • Consider side efffects • Length of continuation/maintenance treatment

  24. Consider Symptoms and Side Effects NE 5HT Attention Drive Appetite Mood Sleep Loss of pleasure Obsessions Anxiety Cognitions

  25. Selective Serotonin Reuptake Inhibitors (SSRI) • First line treatment • Effective in anxiety • Safe, flat dose response -Escitalopram - ? More efffective than citalopram - Fluoxetine – long t1/2, potent inhibition CYP - Paroxetine – short t1/2, discontinuation - Sertraline – mild CYP inhibition

  26. Selective Serotonin Reuptake Inhibitors (SSRI) • Common adverse effects - nausea, vomiting, abdo pain, diarrhoea - sweating - headache - agitation, insomnia, tremor - hyponatraemia (SIADH) elderly, female, - discontinuation syndrome (paroxetine) - sexual dysfunction

  27. Tricyclic Antidepressants (TCA) • Probably more effective than SSRI • S/E Anti chol, anti adren, anti hist action • Cardiotoxic OD, QT prolongation • Weight gain long-term • Doses prescribed too low - Amitriptyline – sedation, anti chol, ↓BPpostural - Clomipramine – similar s/e, 5HT anxiety/OCD - Loferpramine – less cardiotoxic, sedative - Nortriptyline – less s/e, elderly

  28. Monoamine Oxidase Inhibitors (MAOI) • Mode of Action - Block MAO A (Nad/5HT) and B (Dop/TYP) - Avoid tyramine containing substances- ↑↑BP • Clinical Potency - Best for atypical or resistant depression - Withdrawal 2 weeks, withdrawal effects, 5HT syndroms - Mocclobemide – Reversible MAO A inh - Phenelzine/tranylcypromine – irreversible inh, non selective

  29. Monoamine Oxidase Inhibitors (MAOI) • NB Lots of S/E MCQ answer yes - anti cholinergic/anti adrenergic/anti histamine - paraesthesia - headache - hepatotoxicity - leucopenia - hypertensive crises (9%) - sexual dysfunction

  30. Other Antidepressants • Venlafaxine - 5HT/Nad reuptake inhibitor like clomipramine - meta-analysis higher proportion recovery - linear dose response - s/e discontinuation, short t1/2, BP, SSRI like • Mirtazepine - 2 antagonist, wt gain, sedation • Reboxetine - selective Nad antagonist • Duloxetine - 5ht/Nad reuptake inhibitor

  31. Electroconvulsive Therapy • Most effective in TRD (80-85% response) • Well tolerated (6-12 treatments) • Best severe, agitated, elderly, depression • ↑Nad/5HT transmission, Da, PRL +oxyticin release, ↑plasma cortisol, ↑BBB permiability • Adverse effects headache, muscle stiffness, memory, GA

  32. Refractory Depression: Definitions • Failure to respond fully to >1 or several antidepressants (10-30%) • Chronic duration <2 years (10%) - least likely to be effectively treated • Partial response also a problem (>40%)

  33. Management of TRD • Outrule medical cause/medications (e.g. diabetes, hypothyroidism, Cushing’s syndrome, dementia) • Investigate precipitants of depression (e.g. bereavement, marital or family dysharmony, social factors) • Consider comorbidity or misdiagnosis (e.g. anxiety disorders, substance abuse, dementia)

  34. Management of TRD • Psychoeducational - self-help books • Pharmacological - optimise antidepressant treatment - switch class of antidepressant - augment antidepressant • Psychological - CBT/interpersonal psychotherapy prevents early relapse -

  35. Management of TRD: Augmentation • First: low dose lithium 50% response within 1 week • Second: low dose atypical antipsychotics • Third: Triiodothronine (T3), lamotrigine, tryptophan • Fourth: Combine antidepressants

  36. ↑

  37. Anxiety Disorders Types - Generalized Anxiety Disorder - Social phobia - Agoraphobia - Obsessive Compulsive Disorder Treatment - Exposure therapy - SSRIs and Clomipramine, Benzos (<2 weeks)

  38. Bipolar Affective Disorder - Epidemiology • 0.8% prevalence, women later onset (F:M 1.2:1) • Onset early 20s, 50% mania, • Higher rates cities, ?higher social class • Strongly genetic (20% first degree relative) • Very high proportion recur (>90%) • Women more depression BPII>BPI

  39. Management of BAD: Acute • Treatment of mania - Antipsychotics or benzodiazepines - (semi)sodium valproate/lithium • Treatment of bipolar depression - Lithium treatment of choice - Lamotrigine - Antidepressants – risk of inducing mania/rapid cycling

  40. Management of BAD: Maintenance • Moderate dose lithium (0.8-1.2 meq/l) (60-70%), prevents mania and depression • Valproate>Cambamazepine • Better for mania than depression • Lamotrigine • Better for depression than mania • Atypical antipsychotics – recent data

  41. Lithium • Acute and maintenance (depression>mania) • Mode of action - salt, not metabolised, 2/3 excreted by 24 hrs, Avoid NSAID + ACE Inh - G proteins, Na/K ATP ase, cAMP • Side effects - Immediate: dry or metallic taste, diarrhoea, tremor - Nephrogenic diabetes insipitus polydipsia/polyurea (ADH resistance) - Later: Nephropathy (5%), Hypothyroidism (3% pa), weight gain/oed - Toxicity: (.2.0 meq/l) coarse tremor, confusion, ataxia, coma

  42. Other Mood Stabilizers • All are anticonvulsants and act on Na channels and GABA • Valproate - Acute mania, maintenance, rapid cycling - S/E – sedation, weight gain, hair loss, hepatic failure, leucopenia, terato thrombocytopaenia, highly plasma protein bound, displacement • Cambamezipine - Acutr mania, rapid cycling, agression S/E leucopenia (10%) agran, sed apl anaemia, enzyme inducer OCP, rash Stevens-Johnson syndrome -Lamotrigine - Bipolar dsepression S/E rash, headache, nausea, ataxia

More Related