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Flashcards in Antidepressants Deck (33):

the biogenic amine theory of depression.

In other words, deficiency of monoamines such as nor-epi or serotonin in parts of the brain can result in depression whereas excess amounts may result in the affective disorder known as mania.
however, antidepressant therapy generally increases amine levels in the brain for days to weeks before actual therapeutic benefits are gained.


Antidepressant uses

• Moderate to severe depressive illness
• Severe anxiety and panic attacks
• Obsessive compulsive disorders
• Chronic pain
• Eating disorders
• Post-traumatic stress disorder


Antidepressant side effects

All of the antidepressants have a potential for lowering the threshold for seizure activity especially when alcohol is being consumed.

All of the antidepressants have the potential of causing an increase in suicidal thinking and suicidal behavior.


Antidepressant categories

• The major categories of antidepressants include:
• Monoamine oxidase inhibitors (MAOIs)
• Tricyclic antidepressants (TCAs)
• Tetracyclic antidepressants (TeCAs)
• Serotonin reuptake inhibitors (SSRIs)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs)
• Norepinephrine and dopamine reuptake inhibitors (NDRIs)


Monoamine oxidase inhibitors examples

• Tranylcypromine/ Parmate
• Phenelzine/ Nardil
• Isocarcarboxazid/ Marplan
• Selegiline/ Eldepryl

**outdated, most side effects, lethal


Monoamine oxidase inhibitors (MAOI)

• MAOIs are used less commonly than the other antidepressants as they can have serious side effects, including weakness, dizziness, headaches, tremors and the potential for marked hypertension.
• MAOIs can potentiate the effects of sympathomimetics such as norepinephrine.


foods and tyramine

• Tyramine, an amino acid in humans, belongs to the amine family and as such is normally broken down by monoamine oxidase.
cheese (especially aged cheeses), soy products (especially when fermented), certain dried fruits such as raisins, meats and in red wine.

Since gastrointestinal MAO is essential for the adequate breakdown of tyramine, anyone using MAO inhibitors should avoid foods with high levels of tyramine-->serotonin syndrome


Monoamine oxidase inhibitors and crazy SE

• Increased absorption of intact tyramine can cause a potentially toxic elevation of catecholamine levels, resulting in severe headaches, nausea and hypertension.

• Hypertensive emergencies and fatal accelerated hypertension have been reported as a consequence of dietary intake of tyramine in patients taking MAOIs as well as the interaction of MAOIs with other drugs such as any of the narcotics.


Tricyclic antidepressants MOA and uses

• The exact mechanism of action of this class of drugs is not known. Diminishing the reuptake of monoamine neurotransmitters is clearly one of the chief effects.

Subsequent down regulation of postsynaptic receptors may be the true mechanism of action.

• Tricyclic are used to treat obsessive compulsive disorders, enuresis, panic attacks, chronic pain and migraine headaches as well as depression. Insomnia.

The medication is usually taken at bedtime because of sedating side effects.


Tricyclic antidepressants (TCAs) examples

• Amitriptyline/ Elavil
• Amoxapine/ Asendin
• Clomipramine/ Anafranil
• Doxepin/ Doxepin
• Desipramine/ Norpramine
• Imipramine/ Tofranil
• Nortriptyline/ Pamelor
• Protriptylene/ Vivactil


Tricyclic antidepressants SE

• The chief side effects are anti-cholinergic signs and symptoms such as dry mouth, constipation, urinary hesitancy, orthostatic hypotension and sedation.

• Dry mouth, one of the best-known effects, is one of many effects attributed to the effects of the drugs on muscarinic cholinergic receptors.

!!!potentially cardiotoxic and should be avoided in susceptible individuals with heart disease. Dysrythmias, torsade de pointes!!

In contrast to the SSRIs, the cyclic antidepressants can be fatal in doses as little as 10 times the daily dose.
• The toxicity is usually due to prolongation of the QT interval, leading to arrhythmias.


Amitriptyline/ Elavil

• Class: Tricyclic antidepressant (TCA)
• Indication: major depression, bipolar disorder, migraine and tension headaches, chronic pain,
• MOA: CNS modulation of both serotonin and norepinephrine, increasing levels of each of these neurotransmitters.
• Char: PO and IM. Usually taken at bedtime to minimize side effects of drowsiness and dizziness.


Amitriptyline/ Elavil SE

Side effects: Dizziness and marked drowsiness. Anticholinergic effects such as dry mouth, constipation, urinary hesitancy and blurred vision. Stopping treatment abruptly cause withdrawal-like symptoms i.e. nausea, headache, dizziness, lethargy, and flu-like symptoms. This is referred to as discontinuation syndrome.


Tetracyclic antidepressants

• Tetracyclic antidepressants (TeCA’s) are a class of antidepressants that were first introduced in the 1970s.
• They are named after their chemical structure, which contains four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.


Selective serotonin reuptake inhibitors (SSRIs)

• The selective serotonin reuptake inhibitors (SSRIs) are most commonly used- MAJOR DEPRESSION

• The main mechanism of action is the blockade of serotonin reuptake at the pre- synaptic terminal which results in the subsequent increased level of serotonin available for further neurotransmission.

SSRIs have been documented to be helpful in 50% to 70% of patients with major depression.


Selective serotonin reuptake inhibitors SE

• Common side effects include dizziness, ***nausea, headache, fatigue, diarrhea, anxiety, insomnia, and impotence.

• Despite a wide range of potential side effects, the SSRI group of drugs is felt to have the **best benefit/risk ratio of all of the antidepressant drugs.

• Attention is being focused on the possible relationship between SSRI use (with and without abrupt discontinuation) and suicide risk, particularly in adolescents.


Selective serotonin reuptake inhibitors examples

• Citalopram/ Celexa
• Escitalopram/ Lexapro
• Fluoxetine/ Prozac
• Fluvoxamine/ Luvox
• Paroxetine/ Paxil
• Sertraline/ Zoloft


Fluoxetine/ Prozac class, idnication, MOA

• Class: Selective serotonin reuptake inhibitor (SSRI)
• Indication: Major depressive disorder, obsessive compulsive disorder, bulimia and panic disorder.
• MOA: Decreased serotonin reuptake at presynaptic cleft allows for increased serotonin levels in the synapse and increased serotonin made available at post- synaptic receptor sites.

*The FDA states that Paxil should be avoided in children and teens and that in cases of pediatric cases of depressive disorder the antidepressant drug to be used is Prozac.


Fluoxetine/ Prozac char, SE

• Char: PO. Once a day dosing. Half-life of 48 to 72 hours. Generally takes weeks to achieve full therapeutic effects.

• Side effects as noted along with potential for serotonin syndrome with symptoms of fever, agitation, diarrhea and elevated blood pressure. Sexual dysfunction is a very common side-effect with all SSRIs. Common sexual side-effects include lack of interest in sex, impotency and anorgasmia (inability to reach orgasm).


SSRIs and sexual dysfunction

Sexual dysfunction is a very common side-effect, especially with SSRIs. Common sexual side-effects include problems with sexual desire, lack of interest in sex, and anorgasmia (trouble achieving orgasm). Although usually reversible, these sexual side-effects can, in rare cases, last for months or years after the drug has been completely withdrawn. This is known as Post SSRI Sexual Dysfunction.SSRI-induced sexual dysfunction affects 30% to 50% or more of individuals who take these drugs for depression.


Fluoxetine/ Prozacdrug interactions

• Painkillers of the NSAIDs drug family may interfere and reduce the efficiency of SSRIs and may compound the increased risk of gastrointestinal bleeds caused by SSRI use. These agents include:

• Aspirin
• Ibuprofen (Advil, Motrin)
• Naproxen (Aleve)


Serotonin and norepinephrine reuptake inhibitors (SNRIs) examples

• Duloxetine/ Cymbalta
• Desvenlafaxine/ Pristiq
• Milnacipran/Dalcipran
• Nafazodone/ Serzone
• Venlafaxine/ Effexor


Duloxetine/ Cymbalta

• The main uses of Duloxetine are in major depressive disorder, general anxiety disorder, painful peripheral neuropathy and fibromyalgia.

• Although Duloxetine has been shown to reduce the pain associated with diabetic neuropathy, it has not proven effective for the sensations of numbness or tingling or for the other neuropathic complications associated with diabetes.


Duloxetine/ Cymbalta SE

The most common side effects include headache, somnolence, fatigue, nausea, xerostomia, insomnia and erectile dysfunction.
• Black box warning as previously noted: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders.


Trazodone/ Desyrel info

• Trazodone is a tetracyclic antidepressant of the serotonin antagonist and reuptake inhibitor (SARI) class.

• Trazodone also has antianxiety (anxiolytic) and sleep-inducing (hypnotic) effects. Its side-effect profile and potential toxicity are different from those of the original the monoamine oxidase inhibitors (MAOIs) and the tricyclic antidepressants (TCAs).


Trazodone/ Desyrel

off label:
Complex regional pain syndrome
Control of nightmares
Panic disorder
Diabetic neuropathy
Bulimia nervosa Obsessive-compulsive disorder (OCD) Alcohol withdrawal
Erectile dysfunction


Trazodone/ Desyrel

• Class: Tetracyclic
• Indication: Major depressive disorder,
anxiety, panic disorder and insomnia. • MOA: Serotonin reuptake inhibitor and
partial antagonist. Decreased serotonin reuptake at presynaptic cleft allows for increased serotonin levels in the synapse and increased serotonin made available at post-synaptic receptor sites.


Trazodone/ Desyrel: Adverse effects

Sedation, orthostatic hypotension, fatigue, possible cardiac dysrhythmias, possible mania in patients with bipolar disorder. Increased risk of suicide.

***Trazodone appears to be relatively safer than TCAs, MAOIs, and a few of the other second-generation antidepressants in overdose situations, especially when it is the only agent taken.

****Because of its lack of anticholinergic side effects, trazodone is especially useful in situations in which antimuscarinic effects are particularly problematic i.e.., in patients with prostatic hypertrophy, closed-angle glaucoma, or severe constipation


Bupropion/ Wellbutrin

• Class: Norepinephrine and dopamine reuptake inhibitors (NDRI) and nicotine receptor antagonist
• Indication: Major depression, bipolar disorder and attention deficit disorder. Aid in smoking cessation is another indication for Bupropion, although it is marketed under the brand name Zyban when it is used as for that purpose.

• MOA: Blockade of norepinephrine and dopamine reuptake increases the available pool of these amines in the synaptic cleft.


Bupropion/ Wellbutrin SE

• Side effects: Headache, insomnia, dry mouth, tremors, restlessness, agitation, anxiety, sweating and dizziness.
• All of the antidepressents, including the NDRIs, are now being looked at more carefully for the potential of an increase in suicidal behavior.


Bupropion/ Zyban

• Because Bupropion takes five to seven days to reach steady-state blood levels, it is started one week before a smoker's target quit date.
• The recommended dose is 150 mg/day for three days, then 150 mg twice a day.
• Recommended duration of treatment is seven to 12 weeks, although if a smoker is successful in quitting, the drug is approved in the United States for use of up to six months to prevent relapse to tobacco.


Folic acid and depression

• A substantial body of literature suggests that depression may be associated with folate deficiency and that patients with folate deficiency either experience a later onset of action, diminished improvement or higher chances of relapse when taking antidepressants.

• Levomefolic acid (also referred to as methyltetrahydrofolate or 5-MTHF) is the active form of folic acid.

• Methyltetrahydrofolate acts as a co- enzyme modulator in the synthesis of the three monoamines: dopamine, serotonin and norepinephrine.

• Some studies have shown that adequate folic acid levels has been linked to the therapeutic response to SSRIs.
• A subset of patients has shown an improved response to treatment with an SSRI after supplementation with folic acid, folinic acid or MTHF.


Levomefolic acid/ Deplin

• MTHF is marketed in the United States as a so called “medical food” with the brand name, Deplin.
• Deplin comes in two dosages, 7.5 mg and 15 mg of L-methylfolate and is available by prescription only.
• Deplin is approved by the FDA as being indicated for the management of suboptimal folate levels in depressed patients.