PSYCHOPHARMACOLOGY

1. Hakan Atalay Psychiatrist Yeditepe University Hospital PSYCHOPHARMACOLOGY

2. Place and Date of Birth:Ankara, 01.10.1964 Universirt: 1979-1985: Medical School of Ankara University 1986-1987: Compulsory Service at the Outpatient Service of the Ministry of the National Education in Niğde 1987-1991: Specialty Training at Bakırkőy Neuropsychiatric Hospital in Istanbul Dissertation Thesis: Search for the Symptoms of Complex Partial Seizure in Patients with Bipolar Mood Disorder 1992-1995: Psychiatrist at the Bakırkőy Neuropsychiatric Hospital 1995-1997: Psychiatrist at the Balıklı Rum Hastanesi 1998-2001:Psychiatrist at the Beyoğlu Research and Training Hospital 2001-2005: Psychiatrist at the Haydarpaşa Numune Research and Training Hospital 2005: Psychiatrist at the Psychiatry Department of Yeditepe University Hospital Curciculum Vitae

3. HISTORY • 1845 – Hashish intoxication • 1869 – Clorale hydrate • 1875 – Cocaine (Freud)‏ • 1882 – Paraldehyde • 1892 – Research with morpine, ether, alcohol and paraldehyde • 1903 – Barbiturates • 1917- Malaria fever therapy in psychosis

4. HISTORY • 1922- Barbiturate induced coma • 1927 – Insulin shock for sch • 1931 – Reserpine for sch • 1934 – Pentylentetrazole-induced convulsions • 1936 – Frontal lobotomies • 1938 – ECT • 1940 – Phenitoin as anticonvulsant • 1943 – LSD synthesized

5. HISTORY • 1949 – Liyhium • 1952 – Chlorpromazine • 1955 – TCAs and MAOIs • 1960 – Chlordiazepoxide

6. Classification • There has never been and still is not a consensus about how to classify psychotropic drugs. The terminology describing it is continually evolving. • As a rule, agents are organized according to structure (e.g., tricyclic), mechanism (e.g., MAOI), history (e.g., first generation, traditional), or uniqueness (e.g., atypical).

7. Classification • This lack of consistency in the classification of psychotropics causes confusion, but a more fundamental limitation is that drugs continue to be defined by their major indications. • For example, the standard categories of drugs are (1) antipsychotic drugs or neuroleptics used to treat psychosis, (2) antidepressant drugs used to treat depression, (3) antimanic drugs or mood stabilizers used to treat bipolar disorder, (4) antianxiety or anxiolytic drugs used to treat anxious states or used at higher doses, and (5) hypnotic agents to promote sleep.

8. Classification • Describing psychotropic drugs as diagnosis specific ignores the fact that, over time, most agents accumulate multiple therapeutic applications. For example, antidepressant drugs, in fact, have a wide spectrum of action. Agents such as the SSRIs and venlafaxine (Effexor), although still mainly used to treat depression, have also gained FDA approval as treatments for disorders as diverse as panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and premenstrual dysphoric disorder.

12. SSRIs • Fluoxetine (Prozac)‏ • Sertraline (Lustral)‏ • Citalopram (Cipram)‏ • Escitalopram (Cipralex)‏ • Paroxetine (Paxil)‏ • Fluvoxamine (Faverin)‏

17. * Orgasmic difficulties Neuropsychiatric * Headache * Anxiety Side-effects • GIS: • * nausea • * vomiting • * anorexia • * weight loss • * dry moouth • Sexual: • * Lower libido

18. TCAs • Amitryptiline (Laroxyl)‏ • Imipramine (Tofranil)‏ • Chlomipramine (Anafranil)‏ • Dothiepin • Maprotylin (Ludiomil)‏ • Mianserin (Tolvon)‏ • Opipramol (Insidon)‏

21. Arrhytmias OVERDOSE Cardiotoxic Respiratory failure Seizures Coma Side-effects • ANTICHOLINERGIC • Dry mouth • Blurred vision • Constipation • Urinary retention • Drowsiness • CARDIOVASCULAR • Postural hypotension

22. MAOIs • Irreversible: • Phenelzine • Isocarboxide • Reversible: • Moclobemide (Aurorix)‏

24. Weight gain SEXUAL Anorgasmia HEPATIC Hepatotoxic Side-effects • CARDIVASCULAR • Postural hypotension • Arrhytmias • NEUROPSYCHIATRIC • Drowsiness • Insomnia • Headache • GI • Increased appetite

25. Serious side-effects • Hypertensive crisis (due to interactions between MAOIs and tyramine-containing compaouns)‏ • 5-HT syndrome (due to interactions between MAOIs and 5-HT-enhancing drugs)‏ • (Less common with RIMAs)‏

26. Others: • NRI: Reboxetine (Edronax)‏ • SNRI: Venlafaxine (Efexor), Milnacipran (Ixel), Duloxetine (Cymbalta)‏ • NDRI: Bupropion (Zyban)‏ • Mirtazapine (Remeron), Trazodone (Desyrel), Thianeptine (Stablon: Selective Serotonine Reuptake Enhancer - SSRE)‏

27. Nor-adrenerjik Spesifik Serotonerjik Antidepresan (Mirtazapin)‏

28. ANTIPSYCHOTICS • TYPICALS • - Phenothiazines (Chlorpromazine, fluphenazine, thioridazine)‏ • - Butyrophenones (Haloperidol)‏ • Thioxanthine (Flupentixol)‏ • Benzamide (Sulpiride)‏ • ATYPICALS • Clozapine, olanzapine, risperidone, quetiapine, aripiprazole, sertindole, ziprasidone, paliperidone,...

30. Side-effects • EPS: • Parkinsonism • Acute dystonia • Tardive dyskinesia • Akathisia • HYPERPROLACTINEMIA • Impotence • Amenorrhea

31. Side-effects • CHOLINERGIC BLOCKADE • Dry mouth • Blurred vision • Urinary retension • ALPHA ADRENERGIC BLOCKADE • Postural hypotension • HISTAMINERGIC BLOCKADE • Sedation

32. NMS • Autonomic instability • Hypertermia • Raised creatinine phosphokinase • Coma

33. Other side-effects • Cholestatic jaundice (phenothiazines)‏ • Photosensitivity • Cardiac toxicity • - arrhytmias (QT prolongation)‏

34. Side-effects with atypicals • Reduced propensity to EPS • DM (All)‏ • Weight gain (All)‏ • Postural hypotension (All)‏ • Aganulocytosis (Clozapine)‏ • Hyperprolactinemia (Risperidone)‏ • Sedation (Olanzapine)‏ • QT prolongation (Ziprasidone)‏

35. ANXIOLYTICS • Long-acting: • Diazepam (Diazem)‏ • Moderate: • Alprazolam (Xanax)‏ • Lorazepam (Ativan)‏ • Short-acting: • Triazolam (Halcion)‏ • Midazolam (Dormicum)‏

37. INDICATIONS • Anxiety • Insomnia • Alcohol withdrawal • Status epilepticus • Premedication

38. Side-effects • Drowsiness • Dependence and tolerance • Withdrawal syndrome • CAUTION: • * Respiratory depression • * Hepatic impairment

39. Mood stabilisers • Lithium • Sodium valproat • Carbamazepine • Lamotrigine

40. Nephrogenic DI Renal scarring Hypothyroidism Ca disturbance T-wave inversion Leucocytosis Lithium – side effects • Weight gain • Fine tremor • Muscle weakness • Oedema • Diarrhoea • Nausea • Vomiting • Metallic taste

41. Lithium contraindications • Pregnancy • Renal disease • Cardiac disease • Addison's disease • Untreated hypothyroidism

42. Sodium Valproate • Prevents GABA reuptake so enhances GABA-inhibitory transmission. • Reduces concentration of aspartate – an excitatory transmitter/ • Blocks voltage-gated sodium channels/

43. Valproate side-effects • Nausea • Vomiting • Weight gain • Rarely hepatic failure • Pancreatitis • Pancytopenia

44. Clozapine • Has a 3% risk of agranulocytosis. • Any patient presenting with fever, sore throat or infection requires FBC to check for neutropenia • If neutropenic, immediately stop clozapine.

45. Lithium Toxicity • Low therapeutic index, so must be regularly monitored. • Severe nausea, vomiting, cerebellar signs, confusion, muscular twitching, spasticity, choreiform movements, convulsions, slurred speech, drowsiness, coma, death • Serum lithium level • Stop lithium, give oral fluids, control convulsions with diazepam, haemodialysis for severe poisoning

46. NMS • Hyperthermia, fluctuating level of consciousness, muscular rigidity, autonomic dysfunction with pallor, tachycardia, labile BP, sweating and urinary incontinence • Stop antipsychotic. Cardiovascular and respiratory support. Cooling. Bromocriptine may be used. • Usually lasts for 5-7 days and may require transfer to ITU. • 20% mortality.