CNS 3 Antidepressants

First generation antidepressants

older antidepressant agents

Second generation antidepressants

newer, first ling antidepressant agents

Tricyclic antidepressants (TCAs)

MOA - potentiate effect of serotonin and norepinephrine and block ACH in the CNS - 1st generation antidepressant

Before giving TCAs, assess…

cardiovascular history - increased risks with CV disease and elderly

Administer the total daily dose of the TCA at…

HS - aids sleep (sedative) - most minor side effects occur during sleep, increasing adherence

TCAs also treat…

neuropathic pain, insomnia, childhood enuresis, migraine prophylaxis

Toxicity and OD of TCAs

70% fatal due to seizures or cardiac dysrhythmias - no antidote

Side effects of TCAs

dry mouth, constipation, blurred vision, urinary retention and cardiac arrhythmias - postural hypotension (blocks alpha adrenergic receptors) - sedation and weight gain (histamine effect)

Amitriptyline (Elavil)

tricyclic antidepressant

Patient teaching for TCAs

take at bedtime, take several weeks to take effect, do not stop abruptly, sit/stand up slowly to prevent dizziness, avoid driving/operating dangerous machinery until you know how medication will affect you, how to treat dry mouth and constipation, notify HCP for suicidal thoughts or ideations, no alcohol/do not mix with other CNS depressants

Anticholinergic side effects

dry as a bone (constipation), hot as a hare (decreased sweating), tight as a drum (urinary retention), blind as a bat (blurry vision), red as a beet (vasodilation), mad as a hatter (confusion)

MAO inhibitors (MAOI)

multiple food-drug and drug-drug reactions - 2nd line treatment for depression unresponsive to TCAs - MOA - inhibits monoamine oxidase, this increases dopamine, epinephrine and norepinephrine - 1st generation antidepressant

Side effects of MAOI

weight gain, fatigue and sedation, sexual dysfunction, hypotension, muscle cramps, N&V, urinary hesitancy and constipation

Toxicity and OD of MAOI

tachycardia, circulatory collapse, seizures and coma

Never take MAOI with…

other antidepressants (must separate meds by a 2-week washout period), sympathomimetic agents (causes SNS stimulation - OTC cough/cold meds), foods containing tyramine (causes hypertensive crisis and extreme GI upset)

Isocarboxazid (Marplan)

MAO inhibitor

Phenelzine (Nardil)

MAO inhibitor

Tranylcypromine (Parnate)

MAO inhibitor

Selegiline (Emsam)

MAO inhibitor

MAOIs + tyramine =

hypertensive crisis

S&S of HTN crisis

severe increase in BP, tachycardia, shortness of breath, palpitations, chest pain, severe headache, stiff neck, dilated pupils, N&V, sweating and severe anxiety, nosebleeds, severe GI upset

Foods containing tyramine - avoid

smoked, processed, cured foods, aged cheese (yogurt with cultures), fermented foods (sauerkraut, kimchi, pickled vegetables, soy products (tofu, miso)), citrus fruits, bananas, tomatoes, plums, raspberries, alcohol (beer, red wine), chocolate

Patient teaching for MAOIs

dietary restrictions/no tyramine (eat foods as fresh as possible, when discontinued wait 2 wks before adding tyramine back into diet), discuss any OTC meds/supplements with HCP before taking (St. John’s Wort, meds for weight loss, cold/flu remedies - cough syrup, decongestants, etc.), sit/stand up slowly, report S&S of HTN crisis to HCP immediately, no alcohol

Serotonin

a neurotransmitter (hormone) affecting mood and memory

Antidepressants/first line agents

2nd generation antidepressants - affect serotonin - multiple food-drug and drug-drug interactions - most highly bound to albumin (warfarin, phenytoin)

Selective serotonin reuptake inhibitors (SSRIs)

fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil) - no grapefruit

Serotonin antagonist/reuptake inhibitors (SARIs)

trazodone (Desyrel)

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

venlafaxine (Effexor), duloxetine (Cymbalta)

Serotonin-norepinephrine disinhibitors (SNDIs)

mirtazapine (Remeron) - multifaceted MOA - alpha₂ receptor antagonist to help release norepinephrine and serotonin - blocks H1 histamine receptors, causing sedation and appetite stimulation - hase fewer sexual SE

Side effects of antidepressant first-line agents

N&V, agitation, anxiety, insomnia, tremor, sexual dysfunction (70%), tension HA, dry mouth, sweating, weight gain, diarrhea, bleeding, cystitis, serotonin syndrome

Serious toxic reaction when given with SSRIs

tryptophan, MAOIs, amphetamines, lithium, ecstasy, LSD, cocaine, dextromethorphan, some TCAs, venlafaxine, buspirone

Patient teaching for first-line agents

take in the morning, may take 4-6 weeks for full effects, do not take St. John’s Wort

SHIVERS memory tool for serotonin syndrome

shivering, hyperreflexia and myoclonus, increased temperature, vital sign instability, encephalopathy, restlessness and incoordination, sweating (diaphoresis)

Serotonin syndrome cognitive S&S

confusion, hypomania, hallucinations, agitation, delirium, coma

Serotonin syndrome autonomic S&S

shivering, sweating, hyperthermia, hypertension, tachycardia, nausea, diarrhea

Serotonin syndrome somatic S&S

ataxia, myoclonus, twitching, hyperreflexia, rigidity, tremor, ataxia

Serotonin syndrome severe S&S

hyperpyrexia (excessively high fever), cardiovascular shock, death

Norepinephrine-dopamine reuptake inhibitors (NDRIs)

bupropion (Zyban, Wellbutrin) - does not cause sexual dysfunction or weight gain - assess for history of seizures (lowers seizure threshold) - take in morning (can cause insomnia) - do not take with eating disorders (can cause weight loss)

Selective norepinephrine reuptake inhibitors (NRIs)

atomoxetine (Strattera) - Rx ADHD if stimulants not tolerated - takin in morning (can cause insomnia)

Common side effects of Strattera

dizziness, irritability, N&V, insomnia, constipation, dry mouth, decreased appetite

All antidepressants have a…

delayed onset of effectiveness of several weeks - discontinue slowly

Antidepressant withdrawal

anxiety, insomnia or vivid dreams, HA, dizziness, tiredness, irritability, flu-like symptoms, electric shock sensations, return of depression symptoms

Space antidepressants and MAO inhibitors…

14 days apart

Black box warning

antidepressants increase risk of suicidal thinking and behavior in children, adolescents and young adults (monitor for suicidal ideation)

Antidepressants may precipitate…

manic episodes with bipolar disorder or psychotic episode with schizophrenia

All antidepressants may need…

additional form of birth control if on oral contraceptive agents