NERVOUS SYSTEM 4

Nonphenothiazines: Conventional (Typical) Antipsychotic Drugs Agents: Haloperidol (Haldol), loxapine (Loxitane), thiothixene (Navane), pimozide (Orap) MOA: Blockade of dopamine receptors >> serotonin receptors Adverse Effects: Extra-pyramidal symptoms, sedation, drowsiness, dizziness, QTc prolongation, orthostatic hypotension, urinary retention, tardive dyskinesia, neuroleptic malignant syndrome, tremor Comments: Alleviate “positive” schizophrenia symptoms Equally effective as phenothiazines Less sedating than phenothiazines Reduce dose in liver impairment

Antipsychotics: Adverse Effects 1. Extrapyramidal symptoms • Dystonias (head and neck) • Akathisia • Restless, compulsive movements; constant pacing, etc. • Pseudo-Parkinsonism • Haloperidol (Haldol) > Chlorpromazine (Thorazine) > thioridazine (Mellaril) 2. Anticholinergic effects • Dry mouth, blurred vision, urinary retention, tachycardia • Chlorpromazine (Thorazine) = thioridazine (Mellaril) > haloperidol (Haldol) • [Agents that cause the MOST EPS cause the LEAST anticholinergic effects]

Antipsychotics: Adverse Effects 1. Tardive dyskinesia • Uncontrolled, bizarre, involuntary movements of the tongue, face, lip smacking, puffing cheeks, etc. due to hypersensitivity of DA receptors 4. Orthostatic hypotension 5. Sedation – due to blocked H1 receptors centrally • Chlorpromazine (Thorazine) = thioridazine (Mellaril) > haloperidol (Haldol) 6. Sexual dysfunction 7. Neuroleptic malignant syndrome 8. Agranulocytosis

Atypical Antipsychotics Agents: Aripiprazole (Abilify), asenapine (Saphris), clozapine (Clozaril), iloperidone (Fanapt), lurasidone (Latuda), olanzapine (Zyprexa), paliperidone (Invega), quetiapine (Seroquel), risperidone (Risperdal), ziprasidone (Geodon) MOA: Blockade of serotonin receptors > blockade of dopamine receptors Adverse Effects: Tachycardia, sedation, dizziness, headache, light-headedness, somnolence, anxiety, hostility, insomnia, nausea, dry mouth, constipation, akathisia, extrapyramidal symptoms, neuroleptic malignant syndrome, QTc prolongation, weight gain, diabetes Comments: Improves both positive and negative symptoms Much less EPS vs. typical antipsychotics Fewer side effects compared to typical antipsychotics Clozapine: monitor CBC, Clozaril National Registry

Antidepressants • Depression – mood state characterized by diminished interest in normal activity, fatigue, feelings of sadness and impaired concentration nearly every day • Psychodynamic causes • Cognitive causes • Biochemical theories • Antidepressants work by either: • ↑ NE or 5-HT in the synapse by blocking reuptake OR by • Inhibiting degradation of 5-HT or NE by inhibition of monoamine oxidase (MAO)

Selective Serotonin Reuptake Inhibitors (SSRIs) Agents: Citalopram (Celexa), escitalopram oxalate (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), vilazodone (Viibryd) MOA: Highly selective blockade of serotonin Adverse Effects: Nausea, dry mouth, insomnia, somnolence, headache, anxiety, GI disturbances, dizziness, anorexia, fatigue, sexual dysfunction, suicidal ideation, serotonin syndrome, SJS Comments: Generally considered as first line therapy Many applications: OCD, anxiety, PTSD, others Well tolerated, but many drug-drug interactions Black Box Warning: increased risk of suicidal thinking/behavior Onset of effect: 4-6 weeks

Serotonin-norepinephrine Reuptake Inhibitors (SNRIs) Agents: Duloxetine (Cymbalta), Desvenlafaxine (Pristiq), venlafaxine (Effexor) MOA: Moderately selective blockade of norepinephrine and serotonin Adverse Effects: Insomnia, nausea, dry mouth, constipation, hypertension, dizziness, somnolence, sweating, agitation, blurred vision, headache, tremor, vomiting, drowsiness, increased appetite, orthostatic hypotension, sexual dysfunction, suicidal ideation, serotonin syndrome Comments: Other applications: pain disorders, fibromyalgia Several drug-drug interactions Black Box Warning: suicidal thinking/behavior Withdrawal syndrome if stopped abruptly Onset of effect: 4-6 weeks

Serotonin Antagonists Agents: Nefazodone (Serzone), trazodone (Desyrel) MOA: Inhibition of serotonin receptor Adverse Effects: Insomnia, nausea, dry mouth, constipation, dizziness, somnolence, sweating, agitation, blurred vision, headache, tremor, vomiting, drowsiness, increased appetite, orthostatic hypotension, sexual dysfunction, suicidal ideation, serotonin syndrome, QTc prolongation Comments: Several drug-drug interactions Black Box Warning: suicidal thinking/behavior Withdrawal syndrome if stopped abruptly Other applications: insomnia (trazodone) Onset of effect: 4-6 weeks

Atypical Antidepressants Agents: Bupropion (Wellbutrin), mirtazapine (Remeron) MOA: Enhances norepinephrine and dopamine activity Adverse Effects: Insomnia, nausea, dry mouth, dizziness, somnolence, sweating, agitation, blurred vision, headache, tremor, vomiting, drowsiness, weight gain, orthostatic hypotension, sexual dysfunction, suicidal ideation, serotonin syndrome, seizures Comments: Several drug-drug interactions Black Box Warning: suicidal thinking/behavior Withdrawal syndrome if stopped abruptly Bupropion lowers the seizure threshold Onset of effect: 4-6 weeks