Antidepressants Neuroleptics Lesson 20 Unipolar Depression Major Depressive

Antidepressants & Neuroleptics Lesson 20

Unipolar Depression Major Depressive Disorder n Extreme sadness & despair l extent & duration important n Prevalence n ufemales 9 -26% umales 5 -12% l 2: 1 females ~

MAOIs n Monoamine oxidase inhibitors utranylcypromine (Parnate), phenelzine, (Nardil) NE, DA, 5 -HT n Dietary restrictions (Cheese Effect) l avoid foods containing tyramine l metabolism amphetamine-like l urisk of cerebral hemorrhages Many drug interactions n Overdose risk ~ n

Nonselective Cyclic Antidepressants n Reuptake inhibitors l DA, NE, & 5 HT l Tricyclic Antidepressants (TCA) u. Imipramine, l Desipramine Tetracyclic u. Maprotiline n Risk of many drug interactions (e. g. , alcohol, neuroleptics, etc. ~

NSCA: Main Side Effects Risk of overdose n Mania or psychosis n Sedation n Anticholinergic syndrome l tremors, dry mouth, weakness, constipation, blurred vision, confusion n Impotence n

Second Generation Antidepressants

SSRIs Selective serotonin reuptake inhibitors l fluoxetine (Prozac, Sarafem) l sertraline (Zoloft) l paroxetine (Paxil) l citalopram (Celexa) l escitalopram (Lexapro) l fluvoxamine (Luvox) n Fewer fx on NE & DA ~ n

SSRIs: Side Effects Fewer than TCAs l lower sympathetic arousal l no anticholinergic fx n Serotonergic syndrome l GI discomfort, anxiety, restlessness, insomnia, etc. n Sexual dysfunction n Low risk of overdose n Equally effective as TCAs ~ n

SSRIs: Pharmokinetics All similar to fluoxetine (prozac) l lipid soluble l high protein binding n Half-life l 2 - 3 days l active metabolite 7 - 15 days n unorfluoxetine ~

Other Selective Reuptake Inhibitors Norepinephrine Dopamine Reuptake Inhibitor (NDRI) l bupropion (Welbutrin) l Also tx bipolar & Smoking cessation (Zyban) n Side fx l less sexual dysfuntion than SSRI l Insomnia l seizures - 150 mg/dose limit l no subjective euphoria, abuse ~ n

Other Selective Reuptake Inhibitors Selective Serotonin Norepinephrine Reuptake Inhibitor (SNRI) l venlafaxine (Effexor) n Serotonin-2 Antagonists/Reuptake Inhibitors (SARI) l 5 HT 2 –R: autoreceptor l Anxiety disorders, bulimia n Noradrenergic/Specific Serotonergic Antidepressant (Na. SSA) l Mirtazapine (Remeron)~ n

Schizophrenia Disordered thoughts & bizarre behavior l 1 percent of population l equal among sexes n Progressive l can only manage symptoms ~ n

Symptoms Positive Symptoms l Thought disorders l Delusions l Hallucinations n Negative Symptoms l Poverty of speech l Poverty of emotion l Social withdrawal ~ n

Neuroleptic Drugs Also called antipsychotics n All Effective l No abuse liability l Low overdose liability n Major side Effects: l Motor impairments l Agranulocytosis ~ n

Patient Populations: Mental Institutions 600 1956 500 400 Thousands of patients 300 200 1900 1930 1960 YEAR 1975

First Generation Neuroleptics Relieve only positive symptoms n Chlorpromazine (Thorazine) l phenothiazines l primarily blocks D 1 & D 2 n Haloperidol (Haldol) l butyrophenones l primarily blocks D 2 n D 2 -R affinity and clinical potency ~ n

Hi Therapeutic effects Lo Spiroperidol Haloperidol Chlorpromazine Strength of D 2 binding

1 st Generation: Pharmacokinetics Administration l Primarily p. o. ; im for rapid effects n 90 -95% depot binding l liver, lungs, adrenals, spleen n Long half-life l Some metabolites active up to 3 mo. n u. No symptoms during this period ucompliance problems ~

Major Side Effects Movement Effects (Extrapyramidal) l Parkinsonism l Akathisia l Tardive Dyskinesia n Agranulocytosis l white blood cells (WBC) l Not frequent, but 50% mortality ~ n

Atypical Neuroleptics n n n Relieve negative & positive symptoms Lower M-PAT risk l tardive dyskinesia Atypical neuroleptics l affinity for D 2 -R l 5 HT antagonism ~

Atypical Neuroleptics Clozapine Clozaril l Agranulocytosis n Risperidone Risperdal l agranulocytosis; M-PAT n Aripiprazole (Abilify) l depression ~ n