Psychopharmacology

1. Psychopharmacology Khalid Bazaid, MB BS, FRCPC Assistant Professor Child & Adolescent Psychiatrist Department of Psychiatry College of Medicine King Saud University

2. Outlines The role of psychotropic in the mental health and its therapeutic indications Identify specific cautions to be aware of the various psychotropic medications Discuss the adherence to medication treatment Psychotropic Medications Classifications

3. Psychopharmacology • The aim is learn how to choose a psychotropic drug that is more: • Effective • Less toxic • Better-tolerated • The most targeted therapeutic agents

4. Psychotropic Drugs Focus of all mental activity is the CNS (brain) Origin of psychiatric illness caused by many factors: Genetics Neurodevelopment factors Endocrinologic e.g. Hypothyroidism Autoimmune system (infections) Drugs Psychosocial experiences, stressors … etc. To date …Theories behind use of psychotropic drugs focuses on neurotransmitters and their receptors Psychotropic drugs act by modulating neurotransmitters

5. Use of psychotropic medications Relieve or reduce symptoms/signs of dysfunctional thoughts, moods, or actions of mental illness Improve client’s functioning Increase compliance to other therapies

6. Therapeutic Effects of Psychotropic Medications Do not “cure” Relieve or decrease symptoms Prevent or delay return of S/S Cannot be used as the sole treatment for disorders Need informed consent before starting Are broad spectrum and have effects on a large number of S/S Initial effects are sedative in nature May take weeks for effects to be seen

7. Reasons for Non- adherence: Medications are expensive Unpleasant side effects Feel better and decide no longer need Stigma associated with having a mental illness and taking medications Paranoia or fears about medication usage particularly addition

8. Encouraging Compliance to Medication Regimen Follow-up appointments With client to verify that client understands: the purpose, proper administration, intended effects, side and toxic effects of, and how to treat problems associated with medications Appropriate lab tests must be conducted to prevent complications and assure correct levels of drugs Encourage clients to participate in medication groups Can use injections of antipsychotics which will last from 2-4 weeks if clients are non-compliant

9. Efficacy of Psychotropics with Children & Elderly Use with great caution Start low and go slow for both elders and children Children are faster metabolizer whereas elders have decrease liver & renal function Risk of injuries and falls with elderly

10. Client & Family Teaching Purpose of the meds and benefits, side effects and how to treat SE What S/S indicate a toxic effect, and how to treat, and whom to call. Specific instructions about how to take the medications

11. Psychotropic Medications Classifications Antipsychotics (Neuroleptics) Mood Stabilizers Antidepressants Anxiolytics (antianxiety) Sedatives Hypnotics Psychostimulants Antihistamines, antimuscarinics, dopamine agonists

12. Psychotropic Medications Classifications … continued • In many instances, drugs have multiple indications: • SSRIs (selective serotonin reuptake inhibitors) are both antidepressants and anxiolytics. • SDAs (serotonin-dopamine antagonists) are both antipsychotics and mood stabilizers. • Psychotropic drugs have also been organized according to structure (e.g. Tricyclic). • mechanism (e.g. monoamine oxidase inhibitor [MAOI])

13. Antipsychotics Schizophrenia Disorders Bipolar disorder Major Depression with psychotic features Tourette’s Syndrome Delirium, Dementia, and Delusions Control of intractable hiccups Aggressive behavior

14. Antipsychotic - Neuroleptics • First generation • Post synaptic D2 receptor. Dopamine receptor antagonists (DRAs) • Low potency: hypotension, sedation, weight gain more anticholinergic less antidopamenergic less EPS. e.g.Mellaril, chlorpromazine • High potency: More antidopamenergic more EPS less anticholinergic e.g. Haldol • Atypical Antipsychotics(2nd and 3rd generation) • D2, D4, 5HT2 • Serotonin dopamine antagonists (SDAs) • Alpha adrenergic, muscarinic receptors e.g. Clozaril Risperdal Zyprexa Seroquel Abilify Geodon Invega Zeldox

15. First Generation Antipsychotic Block predominantly dopamine activity High incidence of abnormal movements little effect on serotonin (Also blocks acetylcholine, norepinephrine to some degree) Blocks the H receptor for histamine results in sedation and weight gain

16. Side Effects of 1st Gen Drugs-1 Dystonia (EPS) spasms of the eye, neck-torticollis, back, tongue-happens within 72 hrs ( reversible) Akathisia (EPS) restlessness Pseudoparkinson - S/S similar to Parkinson's-see in 1-2 weeks. May disappear. TX. With Cogentin Tardive Dyskinesia-bizarre facial and tongue movements (irreversible)

17. Side Effects of 1st Gen Drugs-2 Blurred vision, dry mouth, constipation and urinary retention, tachycardia-anticholinergic S/E Sexual dysfunction Severe dysrhythmias Orthostatic hypotension Agranulocytosis In men can lead to gynecomastia Amenorrhea Galactorrhea photosensitivity & skin rashes Reduction is seizure threshold – Low potency

18. Precautions and/or contraindicated When using 1st Gen Antipsychotics Blood dyscrasias Liver, renal, or cardiac insufficiency CNS depressants, including ETOH Tegretol in conjunction with antipsychotics causes up to 50% reduction in antipsychotic concentrations SSRI’s in conjunction with antipsychotics may cause sudden onset of EPS Don’t give if have: Parkinson's disease, prolactin dependent cancer of the breast Cigarette smoking causes reduced plasma concentrations of antipsychotics Antacids, activated charcoal can reduce the absorption of DRAs Faverin in conjunction with antipsychotics causes increased concentrations of Haldol and Clozaril Beta Blockers in conjunction with antipsychotics cause severe hypotension Antidepressants in conjunction with antipsychotics may cause increased plasma level of both

19. First Generation Antipsychotic Medications Are useful in getting out of control behavior under control quickly. These can be given with lithium to get treat acute mania. Seroquel is effective in the maintenance treatment of Bipolar-Depressive phase

20. Atypical Antipsychotics Action: Blocks dopamine receptors and to a lesser degree serotonin receptors, Also block receptors for norepinephrine , histamine, acetylcholine Nicer drugs and are used more Decrease positive and negative S/S of Schizophrenia Lower Incidence of abnormal movements Biggest S/E is weight gain e.g. Zyprexa

21. Positive & Negative S/S of Schizophrenia Positive: Hallucinations Delusions Abnormal thoughts Bizarre behavior Confused thoughts Negative: Blunted affect Poverty of speech Social withdrawal Poor motivation

22. Atypical Antipsychotics-2nd & 3rd generation: Clozaril (clozapine) low incidence of abnormal movements Most common S/E: Nausea, constipation, sedation, drowsiness, weight gain Other S/E are: hypersalivation, tachycardia, dizziness, seizure risk possible fatal side effect: bone marrow suppression & Agranulocytosis (rare)

23. Atypical Antipsychotics-2nd & 3rd generation - 2 Risperidone Does not cause bone marrow suppression Can cause at higher doses movement disorders Available as a long acting injection Can be used to treat mania Seroquel (Quetiapine) S/E sedation, weight gain and headache Not associated with abnormal movements May cause AV block

24. Atypical Antipsychotics-2nd & 3rd generation - 3 Zyprexa (Olanzapine) does not cause bone marrow suppression Can cause weight gain & hyperglycemia Drowsiness, dry mouth, constipation, and restlessness Geodon(Ziprasidone) Binds to multiple receptor sites Drowsiness, headache, GI upset Can prolong the QT interval-can be fatal if history of cardiac arrhythmias Abilify (Aripiprazole) Dopamine stabilizer Partial agonist at the D2 receptor In areas of the brain with excess dopamine, it lowers dopamine In areas of low dopamine, it stimulates receptors to raise the dopamine level Main S/E are headache, somnolence, agitation, anxiety, insomnia, and GI upset

25. Antipsychotics-Long acting preparation Can be given be given as an IM injection (depot preparations) if have difficulty taking oral meds. Can use lower doses when given IM, so less risk of tardive dyskinesia

26. Neuroleptic Malignant Syndrome Rare, but fatal complication from all antipsychotic drugs See more with 1st generation drugs Severe muscle rigidity High temperature Associated S/S: Tachycardia Hypertension Stupor Coma Abnormal labs including leukocytosis , Elevated Creatinine phosphokinase (CPK) & LFT

27. Mood Stabilizers Used in the treatment of Manic (Bipolar) disorder, and in some forms of depression Drugs used: Lithium and Antiepileptic Drugs

28. Lithium Mechanism of action unknown Alters electrical conductivity potential threat to all body functions that are regulated by electrical currents Can cause polyuria and polydipsa due to Na and K alterations Has the lowest therapeutic index of all psych drugs Have to monitor blood levels

29. Lithium Maintenance blood levels of lithium are usually 0.4-1.3 mEq (toxicity occurs with levels > 1.5 mEq/L) Sign of toxicity is a fine intention tremor that becomes more pronounced and coarse Risk of thyroid & kidney disease If toxic S/S occur discontinue the drug and notify health care provider Lithium should be taken with food Client must eat a balanced diet with normal sodium intake and take in adequate fluid (about 2-3 liters/day). Excretion is via renal system Dehydration and salt restriction can increase lithium levels & cause toxicity. Takes 2-3 weeks for lithium to become effective (may use antipsychotic until therapeutic levels are reached)

30. Signs & Symptoms of Lithium Toxicity Fine hand tremors that progress into coarse tremors Mild GI upset progressing to persistent upset Slurred speech and muscle weakness progressing to mental confusion • Severe Toxicity: • decrease level of consciousness to stupor and finally coma • Seizures, severe hypotension, severe polyuria with dilute urine

31. Lithium Lithium serum concentrations are increased by Flouxetine (Prozac), ACE inhibitors, Thiazide diuretics, and NSAIDs Lithium serum concentrations are decreased by theophylline, osmotic diuretics, and urine alkalinizers

32. Contraindications for Lithium Renal disease Cardiac disease Severe dehydration Sodium depletion Brain damage Pregnancy or lactation Use with caution in the elderly or clients with diabetics, thyroid disorders, urinary retention, and seizures

33. Anticonvulsants/Antiepileptic Drugs Causes an increase in GABA in the CNS-which causes a decrease in anxiety. Reduce the mood swings with bipolar

34. Anticonvulsants/Antiepileptic Drugs Tegretol(carbamazepine)-also used to treat severe pain (i.e. trigeminal neuralgia), cause agranulocytosis and aplastic anemia Depakote(Valproic acid)-can cause hepatic failure, pancreatitis, & thrombocytopenia. Watch for liver failure Klonopin(Clonazepam) Lamictal(Lamotrigine)-can have a rare but fatal dermatological condition

35. Toxic Effects of Anticonvulsants Tegretol can cause agranulocytosis and aplastic anemia Depakote can cause liver dysfunction, hepatic failure, and blood dyscrasias including thrombocytopenia Depakote interacts with drugs that are metabolized by the liver

36. Contraindications for Anticonvulsants Hepatic or renal disease Pregnancy Lactation Presence of blood dyscrasias

37. Psychoeducation when using anticonvulsants Monitor blood levels of mood stabilizers to prevent toxicity Monitor liver, renal function tests and CBCs Depakote must be swallowed whole, not cut, chewed, or crushed to prevent irritation

38. Evolution of Antidepressant Drugs 1980 1950 2000 1970 1990 1960 2009 Nefazodone Phenelzine Phenelzine Imipramine Imipramine Maprotiline Maprotiline Fluoxetine Fluoxetine Escitalopram Valdoxan Duloxetine Mirtazapine Isocarboxazid Isocarboxazide Clomipramine Clomipramine Amoxapine Amoxapine Sertraline Sertraline Mianserine Paroxetine Reboxetine Tranylcypromine Tranylcypromine Nortriptyline Nortriptyline Trazodone Fluvoxamine Venlafaxine Amitriptyline Amitriptyline Tianeptine Citalopram Desipramine Desipramine Bupropion Milnacipran Moclobemide

39. Antidepressants Treatment of depressive moods, including bipolar disease 4 categories: Tricyclics (TCA) MAOI’s SSRI’S Atypical Antidepressants

40. Antidepressant Drugs Tricyclics- Elavil, Tofranil SSRI’s- Lustral, Seroxat MAOI’s- Nardil, Parnate

41. Atypical Antidepressants Inhibits reuptake of serotonin: Trazodone (desyrel) Norepinephrine Dopamine Reuptake Inhibitor (NDRI): Wellbutrin (Bupropion) Sertonin Norepinephrine Reuptake Inhibitor-(SNRI): Effexor (venlafaxine) Cymbalta (duloxetine) Increases release of serotonin & norepinephrine: Remeron (mirtazapine)

42. Atypical Antidepressants Trazodone: alternative to TCA’s, may cause orthostatic hypotension, sedation, and priapism in males Remeron: causes sedation, weight gain, dry mouth, constipation Wellbutrin (zyban): rarely causes sedation, weight Gain, or sexual dysfunction Used for smoking cessation. Most common S/E are headaches, insomnia & nausea May lower seizure threshold

43. Atypical Antidepressants: serotonin norepinephrine reuptake inhibitor (SNRI) SNRI-blocks uptake of serotonin and norepinephrine Drugs include Effexor & Cymbalta Good for clients with anxiety S/E:GI, sexual dysfunction, insomnia, agitation Skipping 1 dose can cause withdrawal S/S Very effective in treating severe depression Cymbalta is effective in treating somatic symptoms e.g. pain

44. Major Indications for Antidepressants Major Depressive disorder Bipolar depression Anxiety disorders: Panic disorder Obsessive-Compulsive Phobic disorders PTSD Substance Abuse Chronic Pain Tourette’s Disorder ADHD Eating disorders Sleep disorders Migraines Enuresis

45. TriCyclicAntidepressant (TCA): Tryptizol, Pamelor, Tofranil, Anafranil, Aventyl, Asendin, Sinequan Blocks the reuptake of norepinephrine and serotonin Tricyclic drugs block the muscarine receptors causing anticholinergic side effects Other side effects: Orthostatic hypotension Sedation Weight gain Confusion-esp. elderly Arrhythmias

46. TCA’s Contraindications Do not mix with ETOH (none of the psych drugs should be mixed with ETOH) Dementia Suicidal clients Cardiac disease Pregnancy Seizure disorders Urinary retention Dose for elderly should be ½ of adult dose TCA’s and MAOIs are effective in treatment of depression are not as safe nor well tolerated as the newer antidepressants Toxic Effects: possibility of cardiac toxicity in overdose

47. SSRI’s Prozac, Lustral, Seroxat, Faverin, Cipralex, Serzone Blocks the reuptake of serotonin into the neuron Are very safe and are not lethal in overdose Good choice with the elderly-very few side effects If used with MAOI’s may cause Serotonin Syndrome: seizure, death If used with TCA’s may cause TCA toxicity Takes 2 weeks to feel effects Side-effect:GI, CNS however the biggest is sexual dysfunction & weight gain Contraindication: Cardiac dysrhythmias

48. MAOI’s Nardil, Parnate Inhibits MAO, thus interfering with breakdown of norepinephrine, dopamine, and serotonin Avoid foods with tyramine (aged cheese, red wine, beer, chocolate, etc.) MAOI’s don’t play well with other drugs!! Toxic effects:hypertensive crises

49. Psychomotor activation Psychosis - Abuse Sexual dysfunction Sedation/drowsiness Activating sideeffects DA reuptake inhibition Weight gain 5-HT2 agonism H1antagonism Blurred vision Nausea 5-HT3 agonism Dry mouth Traditional Antidepressants Ach antagonism Constipation 5-HTreuptake inhibition Sinus tachyardia GI disturbances Urinary retention Activating effects α1 antagonism NE reuptake inhibition Memory dysfunction α2 antagonism Dry mouth Urinary retention Priapism Activating effects Postural hypotension Dizziness Reflex tachycardia Tremor-CV troubles Adverse effets linked with neurotransmitter activity and receptor binding Adapted from Richelson 1993

50. Antianxiety/Anxiolytic Drugs GABA exerts an inhibitory effect on neurons These drugs enhance its effect and produce a sedative effect Therefore reduce anxiety The most common used drugs here are the Benzodiazepines