Download Antidepressants & Neuroleptics

Antidepressants &
Neuroleptics
Lesson 20
Unipolar Depression
Major Depressive Disorder
 Extreme sadness & despair
 extent & duration important
 Prevalence

females
9-26%
males 5-12%

2:1 females ~
MAOIs

Monoamine oxidase inhibitors
tranylcypromine
(Parnate), phenelzine, (Nardil)
NE, DA, 5-HT
 Dietary restrictions (Cheese Effect)
 avoid foods containing tyramine
 metabolism  amphetamine-like

risk
of cerebral hemorrhages
Many drug interactions
 Overdose risk ~

Nonselective Cyclic Antidepressants

Reuptake inhibitors
 DA, NE, & 5HT
 Tricyclic Antidepressants (TCA)
Imipramine,

Desipramine
Tetracyclic
Maprotiline

Risk of many drug interactions (e.g.,
alcohol, neuroleptics, etc. ~
NSCA: Main Side Effects
Risk of overdose
 Mania or psychosis
 Sedation
 Anticholinergic syndrome
 tremors, dry mouth, weakness,
constipation, blurred vision, confusion
 Impotence

Second Generation
Antidepressants
SSRIs
Selective serotonin reuptake inhibitors
 fluoxetine (Prozac, Sarafem)
 sertraline (Zoloft)
 paroxetine (Paxil)
 citalopram (Celexa)
 escitalopram (Lexapro)
 fluvoxamine (Luvox)
 Fewer fx on NE & DA ~

SSRIs: Side Effects
Fewer than TCAs
 lower sympathetic arousal
 no anticholinergic fx
 Serotonergic syndrome
 GI discomfort, anxiety, restlessness,
insomnia, etc.
 Sexual dysfunction
 Low risk of overdose
 Equally effective as TCAs ~

SSRIs: Pharmokinetics
All similar to fluoxetine (prozac)
 lipid soluble
 high protein binding
 Half-life
 2 - 3 days
 active metabolite 7 - 15 days

norfluoxetine
~
Other Selective Reuptake Inhibitors
Norepinephrine Dopamine Reuptake
Inhibitor (NDRI)
 bupropion (Welbutrin)
 Also tx bipolar & Smoking cessation
(Zyban)
 Side fx
 less sexual dysfuntion than SSRI
 Insomnia
 seizures - 150 mg/dose limit
 no subjective euphoria, abuse ~

Other Selective Reuptake Inhibitors
Selective Serotonin Norepinephrine
Reuptake Inhibitor (SNRI)
 venlafaxine (Effexor)
 Serotonin-2 Antagonists/Reuptake
Inhibitors (SARI)
 5HT2 –R: autoreceptor
 Anxiety disorders, bulimia
 Noradrenergic/Specific Serotonergic
Antidepressant (NaSSA)
 Mirtazapine (Remeron)~

Schizophrenia
Disordered thoughts & bizarre behavior
 1 percent of population
 equal among sexes
 Progressive
 can only manage symptoms ~

Symptoms
Positive Symptoms
 Thought disorders
 Delusions
 Hallucinations
 Negative Symptoms
 Poverty of speech
 Poverty of emotion
 Social withdrawal ~

Neuroleptic Drugs
Also called antipsychotics
 All Effective
 No abuse liability
 Low overdose liability
 Major side Effects:
 Motor impairments
 Agranulocytosis ~

Patient Populations: Mental Institutions
600
1956
500
400
Thousands
of patients 300
200
100
1900
1930
1960
YEAR
1975
First Generation Neuroleptics
Relieve only positive symptoms
 Chlorpromazine (Thorazine)
 phenothiazines
 primarily blocks D1 & D2
 Haloperidol (Haldol)
 butyrophenones
 primarily blocks D2
 D2-R affinity and clinical potency ~

Hi
Therapeutic
effects
Spiroperidol
Haloperidol
Chlorpromazine
Lo
Strength of D2 binding
1st Generation: Pharmacokinetics
Administration
 Primarily p.o.; im for rapid effects
 90-95% depot binding
 liver, lungs, adrenals, spleen
 Long half-life
 Some metabolites active up to 3 mo.

No
symptoms during this period
compliance problems ~
Major Side Effects
Movement Effects (Extrapyramidal)
 Parkinsonism
 Akathisia
 Tardive Dyskinesia
 Agranulocytosis
  white blood cells (WBC)
 Not frequent, but 50% mortality ~

Atypical Neuroleptics



Relieve negative & positive symptoms
Lower M-PAT risk
  tardive dyskinesia
Atypical neuroleptics
  affinity for D2-R
  5HT antagonism ~
Atypical Neuroleptics
Clozapine Clozaril
  Agranulocytosis
 Risperidone Risperdal
  agranulocytosis;  M-PAT
 Aripiprazole (Abilify)
  depression ~
