Antidepressants

SSRIs (Selective Serotonin Reuptake Inhibitors)

• fluoxetine (Prozac)
• fluvoxamine maleate (Luvox)
• paroxetine (Paxil)
• citalopram (Celexa)
• sertraline (Zoloft)

• anxiety disorders: panic, OCD, PTSD, social phobia
• bulemia
• PMS
• chronic pain
• pediatric complications
• more selective for serotonin
• decreased toxicity compared with TCAs
• less risk of interactions compared with MAOIs
• decreased suicide risk

• block reuptake in the presynaptic cell, leading to increased serotonin in the synapse
• increased 5-HT signaling on presynaptic autoreceptors is thought to transiently decrease serotonin production; downregulation of autoreceptors then leads to increased production
• may also increase neurogenesis in the hippocampus

side effects

• nausea, vomiting, diarrhea
• sexual
• changes in weight
• serotonin syndrome - drug interactions maybe (MAOIs)
  • tachcardia
  • diaphoresis
  • hypertension
  • hyperthermia
• may cause suicide in children and adolescents, though effect is minimal

• SSRIs inhibit liver CYP 2D6, which is responsible for activation of codeine to morphine
• do not combine with MAOI's or TCA's due to risk of serotonin syndrome

 

 

 

 

NDRI (Norepinephrine and Dopamine Reultake Inhibitor)

• buproprion

TCAs (Tri-Cyclic Antidepressants)

• amitriptyline
• nortriptyline
• imipramine
• clomipramine

uses:

• melancholic depression
• OCD (clomipramine)
• bedwetting
• ADD

mechanism:

TCAs inhibit NE, 5-HT, and sometimes DA re-uptake. Acting as muscarinic antagonists, they also have various anti-histamine effects.

 

side effects

• antimuscarinic side effects: constipation, urinary hesitation, blurred vision, confusion, dry mouth
• a month's supply will kill you (arrhythmias)

• narrow therapeutic window

atropine-like side effects:

• sedation
• tremors, insomnia
• constipation, dry mouth
• hypotension
• psychosis
• withdrawal symptoms
• weight gain

• increased suicidal tendenencies in the young

• combination with SSRIs or MAOIs can lead to serotonin syndrome

 

Overdose

well and rapidly absorbed; quick onset

large volume of distribution, higher concentrations of drug in tissue cf blood; so not dialyzable

sodium channel blockade is most dangerous effect

CVS, CNS effects parallel

coma in 24-48 hours

treat with best supportive care, charcoal, sodium bicarbonate

sodium is the biggest treatment to restore CV function

 

 

SVT, icreased QRS >0.1, right axis deviation

 

SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors)

• duloxetine
• venlafaxine

 

side effects: nausea, vomiting, insomnia, sleepiness, constipation, dry mouth, tremor, anxiety, agitation, abnormal vision, sexual dysfunction, headache

 

• interactions with drugs that affect 5-HT, such as SSRIs, St John's Wort, may lead to serotonin syndrome

 

MAOIs (Monoamine Oxidase Inhibitors)

• phenelzine
• tranylcypromine

MAOIs blocks major interneuronal degradative pathway for amine transmitters NE, DA, 5-HT irreversibly. This induces the accumulation and release of NTs.

 

Uses:

• moderate/severe depression, not responding to SSRI
• atypical depression
• chronic pain
• enuresis

Some cheeses, red wine, and fermented foods are high in tyramine. Blockade of liver MAO results in high blood levels of tyramine, which can cross the BBB and induce mass release of NE, resulting in hypertensive crisis.

 

 

The clinical effects of MAOIs last for 1-3 weeks after drug has disappeared from blood.

 

long term

• agitation, neuromuscluar excitability
• shock

 

serotonin syndrome

• SSRIs/TCA/SNRI, meperidine, L-tryptophan, L-dopa, epinephrine/norepinephrine, stimulants, hypoglycemic agents, dextromethorphan