PHAR 752 Antidepressant Drugs Flashcards Preview

Pharmacy School 2016-17 > PHAR 752 Antidepressant Drugs > Flashcards

Flashcards in PHAR 752 Antidepressant Drugs Deck (43):

Symptoms of Depression

-Gloomy, hopeless, helpless
-Worry, dread, doom
-Worthlessness and guilt
-Inability to concentrate and slowed thinking
-Suicidal ideation (10-15% will attempt suicide)

Emotions and Pain (pain, sadness, anxiety, irritability, anger and anhedonia apathy)

Behaviors (loss of appetite and libido, disturbanecs in diurnal rhythm, insomnia, inability to act, social withdrawal)


Unipolar vs Bipolar depression

Bipolar characterized by manic phase (antidepressants can precipitate this phase)

Mood stabilizers often used for bipolar phase


Unipolar/Major Depression

5-15% of US adult population impacted

Major economic burden

2-3 times more common in women

Episodes can last 4-12 months with an average onset age of 30 years | usually recurrent

40% have a genetic disposition and 80% respond to treatment


Depression subcategories

Mild, moderate and severe (medication works best for moderate to severe)

Reactive depression (normal response to circumstances)

Agitated or atypical depression (fear, insomnia, extreme irritability, and restlessness)

Dysthymia (low level, long term melancholy - usually over 2 years)

Premenstrual dysphoric disorder (hormone driven?)

Post-partum depression (can occur up to 6 months following delivery)

Psychotic depression (perception of reality becomes altered)

Seasonal affective disorder


Treatment options for depression

Talk therapy
Light therapy
Exercise (reduces relapse)
Electroconvulsive Therapy (ECT)


Electroconvulsive Therapy Pros/Cons

Effective in resistant depression

Rapidly effective

Disadvantage is confusion and memory loss


Antidepressant Effects

2-6 weeks latency

Improve mood, affect, appetite and sleep

Effective in 70-80% of patients

Taken prophylactically

Also used to treat neuropathic pain


Natural herbal remedy for depression

St. John's Wort


Antidepressants biogenic amine hypothesis

Antidepressants work by extending duration of action of biogenic amines (norepinephrine, serotonin and dopamine) through blockade of reuptake or inhibition of metabolism.

This leads to an elevation in mood.


Norepinephrine deficit depression symptoms

Attention deficit, poor working memory, reduced alertness, low energy and social withdrawal


5-HT deficit depression symptoms

Agitation, appetite disturbance, sleep disturbance, anxiety


Describe antidepressant affects on biogenic amine synthesis

NE or 5HT levels increase within 2-3 hours but effects do not manifest for 2-3 weeks due to receptor and transporter modification in the brain


The integrated hypothesis of antidepressant action

Increases in 5HT or NE transmission will decrease some presynaptic receptors, increasing neurotransmitter release.

Transporter levels also decrease long-term, increasing levels of neurotransmitter in synaptic cleft.

Long-term increases in NE or 5HT transmission will cause changes in the brain (neurogenesis, increased number of synapses, glutamate signaling and improved mood)


Drugs that only target ________ reuptake are not good antidepressants. There must be some inhibition of _________ reuptake.

Norepinephrine | Serotonin


Inhibition of degradation in antidepressants (as opposed to block of reuptake) differs in that..

The transporter is not lost


Potential ultimate effects of antidepressants

Increase brain derived neurotropic factor (BDNF) and neuronal sprouting, primarily in the hippocampus


Cocaine and ketamine

Cocaine is a terrible antidepressant

Ketamine (via infusion) has a lasting antidepressant effect but often causes hallucinations


Tricyclic antidepressants

Block NE and 5HT transporters

Was the standard therapy prior to 1990

Drugs include Imipramine (Tofranil), Amitriptyline (Elavil), Desipramine (Norpramin), Doxepin (Sinequan) and Maprotiline (Ludiomil)

Used for neuropathic pain



Side effects of TCAs

CV effects:
-a1 adrenergic receptor antagonism (increased HR)
-Antagonism of muscarinic cholinergic receptors (increased HR) --> least with doxepin, most with amitriptyline
-NE activation of cardiac b-adrenergic receptors

Other side effects:
-histamine H1 receptor antagonism (sleepiness; worst with amitriptyline and doxepin)
-weight gain
-decreased seizure threshold
-sexual side effects related to 5HT alterations including loss of libido and impotence


TCAs and overdose

Lethal in overdose

Toxic sedative effects when combined with alcohol, benzos and barbiturates

Toxic cardiac effects

CNS anticholinergic psychosis (similar to scopolamine)



Block NE and 5HT breakdown

Irreversible and very long lasting

Includes Phenelzine (Nardil), Tranylcypromine (Parnate) and Isocarboxazid (Marplan)

Used only in cases of treatment resistant or atypical depression (e.g. high anxiety, phobias, hypersomnia, hyperphagia)

Useful in narcolepsy

Watch tyramine intake (wine and cheese)


MAOIs adverse effects

Insomnia followed by daytime sleepiness

Dry mouth

Impotence and loss of libido

Hepatotoxicity associated with phenelzine

Long washout period

Overdose toxicities include hyperthermia (too much serotonin) as well as hypertension, tachycardia and muscular agitation (all from too much NE)


_________ is given in hyperthermia as a result of MAOI

Dantrolene (as seen in co-administration of succinyl-choline with inhaled anasthetic)


MAOI toxic drug interactions

Can dangerously prolong half-lives of oxidatively deaminated drugs

Sympathetic crisis with sympathetic amines

Serotonin syndrome (similar to neuroleptic malignant syndrome): hyperthermia, muscle rigidity, myoclonus, mental disorientation, dose dependent and treated with dantrolene
-->problematic with any drugs increasing serotonergic transmission, including triptans, SSRIs, meperidine (opioid) or dextromethorphan


MAOI toxic food interactions

Aged cheese, aged meats, spoiled meats and fish, sauerkraut, soy sauce, fava beans, banana peels, beers on tap

Have red or white win in moderation (4 oz or less)

Have bottled or canned beers in moderation


MAO-B Inhibitor Antidepressant

Selegiline (Eldepryl or Emsam)

More commonly used with Parkinson's disease

Mechanism: Interferes with dopamine metabolism and may affect serotonin receptors (even though MAO-A is selective for NE and 5HT, MAO-B may still play a role)


Reversible MAO-A Inhibitors as Antidepressants

Some approved outside of US but none currently in the US



First line agents

Block 5HT reuptake

Same therapeutic effects and latency of action as TCAs but much better side effect profile (no affinity for alpha adrenergic, muscarinic, histamine or dopamine receptors)

Fluoxetine, Sertraline, Paroxetine, Fluvoxamine, Citalopram, and Escitalopram




First of SSRIs to be marketed and the best characterized

Most stimulating of SSRIs

Hyponatremia in older patients (as serotonin regulated secretion of vasopressin)


Sertraline and Paroxetine


Zoloft; Paxil

Better for anxiety with depression

Questionable efficacy teens, therefore, don't usually start teens on these two





Shorter half life so less time is needed for wash out


Citalopram and Escitalopram


Celexa; Lexapro

Largest selectivity for SERT over NET of all SSRIs (doesn't really alter efficacy)

QT prolongation limits dosing for Citalopram (usually half of the dose of Escitalopram)

Fewer histamine side effects with Escitalopram


Adverse effects of SSRIs

Nausea, headaches, nervousness and insomnia

Sexual dysfunction in men and women

Hyponatremia from elevated vasopressin


Serotonin syndrome

Suicidal ideation (seems to be tied to age - teens are most at risk, elderly actually have decreased suicidal ideation)


SSRI discontinuation syndrome

Nightmares, insomnia, confusion and vertigo

Irritability, agitation

Electrical sensations (brain zaps, brain shivers, or cranial zings)

Taper dose, symptoms usually resolved after several weeks


SSRI overdose toxicity

Extremely rare

Seizures, leading to death, in combination with other drugs only


Multimodal SSRIs

AKA Serotonin modulators and stimulators

Have affinities for various 5HT receptor subtypes in addition to blocking SERT (e.g. 5HT1A, 5HT2, 5HT3, 5HT7)

Vilazodone and Vortioxetine (few sexual side effects)




Multimodal SSRI


Weaker SSRI but given in higher doses to block SERT

Off label use as a sleep aid

Additionally an H1 histamine and a1 antagonist (sleepiness | orthostatic hypotension and tachycardia)

Has more predictable side effects than others

Off label use in OCD (**belemia)



Venlafaxine (Effexor), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq), Levomilnacipran (Fetzima)

All have affinity for SERT and NET

No affinity for adrenergic or muscarinic receptors

Adverse effects similar to SSRIs (additional side effects from increased NE including mild hypertension, dry mouth, increased HR and dilated pupils)


Atypical antidepressants

Buproprion and Mirtazapine

Do not appear to block SERT

Same efficacy and delayed onset of action as SSRIs



Wellbutrin for depression (causes weight loss in 25% of patients )

Zyban for smoking cessation

MOA is elusive (inhibition of central nicotinic receptors, weak inhibition of NE and dopamine reuptake)
-->theory is that depression is an OCD, and that OCD is a dysfunction of the reward mechanism


Not anticholinergic, antihistamine or sexual side effects reported

Safer for bipolar depression




Good for anxiety with depression

H1 antagonist

Useful for treatment of resistant depression

MOA not well understood:
-may potentiate NE and 5HT release by blocking autoreceptors
-weak NET blocker
-No anticholinergic or sexual side effects


St. John's Wart

Herbal supplement from Hypericum perforatum

MOA unknown

Active ingredient unknown (standardized to levels of hyperforin; extracts also contain polycyclic phenols, hypericin, flavonoids, kampferol and biapigenin)

Meta analysis suggests St Johns Wort is superior to placebo and has similar efficacy to SSRIs in treating depression

*do not use at same time as other antidepressants, especially SSRIs due to serotonin syndrome\

**still takes 6 weeks for action, may be less withdrawal but should still be tapered


Adverse effects of St. John's Wart

Dry mouth, dizziness, sleepiness and some confusion

Photophobia, nausea, and/or diarrhea

Can induce manic episodes in bipolar patients

Mild form of serotonin syndrome may ensue in combination with SSRIs

Induces cytochrome P450 (decreases bioavailability of digoxin, theophylline, cyclosporin, phenprocoumon and other drugs...including oral contraceptives)

Natural remedies are not necessarily any safer than synthetic drugs