Antipsychotics + Antidepressants

First-generation antipsychotics (act on, disorders used on)

-Block D2 receptors, dopamine antagonists

-Uses: Scz, psychotic disorders, more effective on +ive sxs

Low-potency FGAs (names)

-Thioridazine (Mellaril)

-Chlorpromazine (Thorazine)

-low-potency = larger dose required, and block muscarinic ACh receptors (not just D2) → anticholinergic SEs

High-potency FGAs

-Haloperidol (Haldol)

-Fluphenazine (Prolixin)

HAL and FLU are highly potent

First-generation antipsychotics side effects

ACh SEs from low-potency FGAs

1.) Anticholinergic

Cutting off dopamine SEs:

2.) Extrapyramidal – esp. high-potency FGAs

3.) (Life-threatening, no D → crash out) NMS, Neuroleptic Malignant Syndrome

Anticholinergic SEs

-most likely from low-potency FGAs (thioridazine, chlorpromazine), sometimes SGAs

-Can’t see, can’t pee, can’t spit, can’t poop → racing heart! (blurred vision, urinary retention, dry mouth, constipation, tachycardia)

Extrapyramidal SEs

-most likely with high-potency FGAs (HALoperidol, FLUphenazine)––dopamine is blocked

-extrapyramidal = involuntary movement; outside of voluntary motor pathways

-D = oil needed for smooth movement, without D → Parkinsonism

-parkinsonism (resting tremor, rigidity, bradykinesia)

-dystonia (twisting, painful posture from involuntary muscle contraction)

-akathisia (inner restlessness)

-tardive dyskinesia

Akathisia

-inner sense of restlessness, need to move

-extrapyramidal side effect, common with high-potency FGAs (HAL and FLU)

Tardive dyskinesia

-Involuntary rhythmic movements of jaw, tongue, face; can also affect limbs and trunk over time

-SE of high-potency FGAs (HAL and FLU)

-tardive = after LT drug use (that block D)

-more common in women and older adults, irreversible for some

-can be life threatening (if muscle spasms disrupt breathing/eating)

Treatment of tardive dyskinesia

-gradually withdrawing from FGA, switching to SGA

-or benzodiazepine (increases inhibitory GABA)

Neuroleptic malignant syndrome

-abrupt cut-off from D supply → crash out

-can happen with withdrawing from Parkinson’s drugs or antipsychotics

FARM

-Sxs: high Fever, Autonomic dysfunction (sweating, high HR), extreme Rigidity, Mental state (confusion, combativeness)

Treatment of NMS

-Stop FGA immediately + supportive therapy (i.e., hydration, cooling)

Second-generation antipsychotics (act on, uses)

-Dopamine-serotonin antagonists (block D2, D3, D4)

-Uses: Scz/psychotic sxs + adjunctive tx for MDD/bipolar (unlike FGAs)

-Effective for +ive sxs (by blocking D2/3/4), and some may help –ive and cognitive sxs of Scz (blocking serotonin/5-HT2A)

-CROQ

Second-generation antipsychotics (names)

CROQ

-Clozapine (Clozaril)

-Risperidone (Risperdal)

-Olanzapine (Zyprexa)

-Quetiapine (Seroquel)

SGA side effects

-less likely to cause extrapyramidal SEs, i.e., tardive dyskinesia

1.) Anticholinergic SEs, NMS

2.) Metabolic syndrome (weight gain, increased diabetes risk, insulin resistance/hyperglycemia; high BP, increased heart disease risk)

3.) Mainly with clozapine: neutropenia and agranulocytocis

Neutropenia and agranulocytocis

-SEs of clozapine

-clozapine pts require regular blood tests

-dangerously low levels of neutrophils (type of WBC)

*potentially life-threatening

-agranulocytocis – even more severe form, near total absence of neutrophils

Third-generation antipsychotics (act on)

-Dopamine-serotonin stabilizers (called partial agonists, but both agonist/antagonist effects)

(Dimmer switch – balances D and S in different parts of brain)

-D2 antagonists in areas where D is high (treats +ive sxs)

-Partial D2 agonists in areas where D is low (treats –ive and cognitive sxs)

-Serotonin antagonists (5-HT2A) and partial agonists (5-HT1A) (treats depression, anxiety, cognitive sxs)

Third-generation antipsychotics (uses, names)

-Uses: Scz, adjunctive tx for MDD/bipolar

ABC

-ARIpiprazole (Abilify)

-BREX-piprazole (Rexulti)

-CARIprazine (Vraylar)

TGA side effects

-less likely to cause FGA SEs (anticholinergic, extrapyramidal/tardive dyskinesia, NMS)

-less likely to cause SGA SEs (anticholinergic, metabolic syndrome)

-Various SEs depend on the TGA:

• akathisia, anxiety

• headache, nausea, fatigue

• aripiprazole may cause addictive gambling, impulse control disorders

SSRIs & Side Effects

-indirect serotonin agonists

-fluvoxamine (Luvox), citalopram (Celexa), escitalopram

-paroxetine (Paxil)

-sertraline (Zoloft)

-fewer SEs than TCAs (less anticholinergic effects, less cardiotoxic)

-anxiety, insomnia, GI disturbance, sexual dysfunction

SNRIs (names and uses)

-venlafaxine (Effexor), desvenlafaxine (Pristiq)

-duloxetine (Cymbalta)

-levomilnacipran (Fetzima)

-Uses: MDD, GAD, social anxiety disorder, neuropathic pain

-may be more effective than SSRIs for severe depression

SNRI Side Effects

-similar to SSRIs, but can elevate BP (d/t effects on N)

-SNRIs may be contraindicated for people with high BP, or heart problems

Discontinuation syndrome

-from abrupt cessation of SSRI/SNRI

-flu-like sxs (headache, nausea)

-mood lability, insomnia

-impaired concentration

Serotonin syndrome

(when SSRI/SNRI combined with MAOI, Lithium, other S drug)

-potentially fatal

-tremors, seizures, high fever, autonomic instability

-agitation, confusion/delirium

-tx = withdraw from S drugs, address the sxs

Tachyphylaxis

-Antidepressant poop-out (seen with SSRI and MAOIs)

e.g., apathy, fatigue, dulled cognitive fx, sleep/sexual dysfunction

-tx = increase dose/another med → switch to SNRI or TCA (reduced tachyphylaxis rates)

NDRI (use and side effects)

-Bupropion

-Use: MDD, smoking cessation

-Side effects:

-skin rash

-agitation, seizures, insomnia (bupropion N/D effects are less helpful for anxiety and insomnia)

-appetite/weight loss

*but few anticholinergic effects and not cardiotoxic (like TCAs)

TCAs (what are they, uses, precautions)

-Inhibit reuptake of S and N, but are also ACh muscarinic antagonists (→ anticholinergic SEs)

-Uses:

• neuropathic pain, pain disorders (nortriptyline and amitriptyline)

• panic, OCD (clomipramine–Anafranil)

*Cardiotoxic (precaution with heart disease)

*Lethal overdose (precaution with suicidality)

*Most likely to induce mania of the antidepressants

TCAs (names)

Tertiary amines: stronger reuptake of S, than N

-clomipramine (Anafranil) – for compulsions (panic, OCD)

-amitriptyline (Elavil) – pain

-imipramine (Tofranil)

-doxepin (Sinequan)

Secondary amines: stronger reuptake of N; fewer SEs (anticholinergic, sedative)

-nortriptyline (Pamelor) – pain

-desipramine (Norpramin)

TCA Side Effects

-Anticholinergic SEs

-Sedative, weight gain, sexual dysfunction

-Cardiovascular/Cardiotoxic (d/t acting on N): high BP, fast HR, orthostatic hypotension

-Lethal overdose

-Secondary amines have fewer anticholinergic and sedative SEs

-most likely to induce mania of the antidepressants

MAOIs (act on, uses, names)

-Increases S/N/D (all three) by inhibition MAO enzyme, which deactivates S/N/D

-Uses: treatment-resistant and atypical depression (sleeping/eating more)

-phenelzine (Nardil)

-isocarboxazid (Marplan)

-tranylcypromine (Parnate)

MAOI Side Effects

(similar to TCA, but not cardiotoxic)

-anticholinergic effects, sedation, sexual dysfunction

-orthostatic hypotension

-hypertensive crisis

Hypertensive crisis

-Sudden dangerous spike in BP

-when MAOI is taken with specific drugs (amphetamines/stimulants, antihistamines/cold med) or tyramine soy boy foods (aged cheese/meats, red wine, beer, ripe bananas)

Sxs: severe throbbing headache, confusion/delirium

-rapid HR, sweating, sensitivity to light

-stiff neck/pain, nausea, vomiting