Chapter 19

Antidepressant Drugs

Psychiatric-Mental Health Nurses Association of the Philippines, Inc. (PMHNAP)

Antidepressant Drugs
Used in the treatment of depression and other disorders. Goals of antidepressant medications are as follows:
o o o o Alleviate depressive symptoms Restore normal mood Prevent recurrence of depression Prevent a swing into mania for bipolar patients

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Biochemical Theory of Depression

Linking of neurotransmitter depletion to depression. Synthesizing of agents that would increase the intrasynaptic availability of certain neurotransmitters, such as norepinephrine, serotonin, and dopamine. Elevations in these neurotransmitter levels occur within hours of treatment initiation. Receptor changes take approximately 2 to 4 weeks and genetic changes even longer.

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Psychopharmacologic treatment
1. Selective serotonin reuptake inhibitors (SSRIs) 2. Norepinephrine and dopamine reuptake inhibitors (NDRIs) 3. Selective serotonin-norepinephrine reuptake inhibitors (SNRIs) 4. Alpha-2 antagonism with 5-HT2 and 5-HT3 antagonism 5. Nonselective inhibition of norepinephrine and serotonin 6. Inhibition of enzymes
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Selective Serotonin Reuptake Inhibitors

Have fewer side effects than TCAs and are far less dangerous than MAOIs. The first-line drugs for treatment of depression. Have fewer anticholinergic, cardiovascular, and sedating side effects. Risk of suicidal thinking & behavior when prescribed to children, adolescents, and young adults. Antidepressant apathy syndrome (AAS)
o lack of motivation, indifference, disinhibition, and poor attention
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Pharmacologic Effect
The antidepressant effect of SSRIs is thought to be linked to their inhibition of serotonin reuptake into neurons. These drugs do not bind significantly to histaminic, cholinergic, dopaminergic, or adrenergic receptors, thus reducing many of the side effects that plague people who are taking TCAs.

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Pharmacokinetics
SSRIs are absorbed in the GI tract. Peak plasma levels are achieved for most of these drugs between 4 and 6 hours. SSRIs are metabolized in the liver and have relatively long serum half-lives. The long half-lives allow once-daily dosing schedules. Both fluoxetine and sertraline have active metabolites that significantly extend their half-lives. Abrupt cessation is associated with the development of specific signs and symptoms.

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Side Effects
Have relatively few anticholinergic, antihistaminic, or antiadrenergic effects; thus, they do not cause the same intensity of side effects associated with TCAs. Dry mouth, blurred vision, sedation, and cardiovascular symptoms are not common. GI symptoms: nausea, diarrhea, loose stools, and weight loss or gain are relatively common. Hyponatremia has occurred with these drugs, mostly in older patients.

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Side Effects
Central nervous system (CNS) effects include headache, dizziness, tremors, anxiety, insomnia, decreased libido, impotence, ejaculatory delay, and decreased orgasm. Anxiety, insomnia, and sexual dysfunction.
o Sexual dysfunction is a major factor in decisions about compliance. With the increasing incidence of premature ejaculation, and some SSRIs are used to delay orgasm in these men.

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Interactions
SSRIs interact with several drugs and some of these interactions are related to SSRI inhibition of the cytochrome P-450 enzyme system. Combining SSRIs and MAOIs has proven to be fatal. This phenomenon is called serotonin syndrome or serotonin toxicity.

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Nursing Implications
Therapeutic Versus Toxic Drug Levels
o SSRIs have a low potential for overdose. Toxic symptoms include nausea, vomiting, tremor, myoclonus, and irritability.

Use During Pregnancy

o SSRIs are pregnancy category B drugs (meaning that risks to the fetus have not been established).

Use in Older Adults

o SSRIs are safe for use in older adults because of the good side-effect profile of these drugs.
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Five Important Issues Related to Antidepressant Use

1. Serotonin syndrome: hyperthermia, rigidity, cognitive impairments, and autonomic symptoms. 2. Antidepressant apathy syndrome: lost of interest in life and the events around them. 3. Antidepressant withdrawal syndrome: Abrupt discontinuation produces withdrawal symptoms.

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Five Important Issues Related to Antidepressant Use

4. Antidepressant loss of effectiveness: Sometimes these drugs just quit working (also known as drug poop out). 5. Antidepressant-induced suicide: These drugs carry a black box warning about suicide; particularly in 18- to 24-year-olds early in treatment.

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Selective Serotonin Reuptake Inhibitors

Citalopram Escitalopram Fluoxetine Fluoxetine/Olanzapine Fluvoxamine Paroxetine Sertraline

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Novel Antidepressants
Bupropion Venlafaxine, Desvenlafaxine, Duloxetine Trazodone Mirtrazine Scopolamine

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Pharmacologic Effects
TCAs block the reuptake of norepinephrine and serotonin, thereby increasing the intrasynaptic levels and alleviating the symptoms of depression. TCAs are significantly more effective for severe depression than were SSRIs. Blocking neurotransmitter reuptake causes greater neurotransmitter availability and thus prolongs the stimulating action. A lag period of 2 to 4 weeks before an antidepressant effect is observed.
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Other Therapeutic Effects

Sedation Lethargy Improved appetite Anxiety reduction Urinary hesitancy

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Pharmacokinetics and Dosing

TCAs are absorbed well from the GI tract and are usually given orally (PO). TCAs are metabolized in the liver, and some metabolites have antidepressant effects. Peak plasma concentrations are reached in 2 to 4 hours; only about 30% to 70% of an oral dose reaches the bloodstream.

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Pharmacokinetics and Dosing

TCAs are highly bound to plasma proteins. Serum levels between 50 and 300 ng/ml are therapeutic. Have relatively long half-lives. A steady state is typically reached in approximately 5 days. All TCAs appear to be equally effective.

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Side Effects
Undesirable side effects of both the peripheral nervous system (PNS) and the CNS. Tertiary amines have more frequent and more severe side effects than secondary amines. PNS side effects
o Anticholinergic, cardiac, and antiadrenergic effects.

CNS side effects

o Sedation and cognitive or psychiatric effects

Suicide
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Suicide
A clear association exists between suicide and depression. Most individuals who commit suicide are found to have demonstrated characteristics of depression. However, antidepressants can energize patients who have been too depressed to act on their suicidal thoughts. TCAs are generally highly toxic, which means that the actual drug a patient is taking to treat depression could be used to overdose and die.
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Suicide
TCAs account for slightly less than 10% of all deaths from intentional drug overdose. 21% of all suicide completers took TCAs, whereas 44% tested positive for novel antidepressants and 35% for SSRIs. Novel antidepressants have a lower potential for lethal overdose and might be better suited for actively suicidal patients.

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Interactions
Central Nervous System Depression
o Increased CNS depression might occur when TCAs are taken with CNS depressants (e.g., alcohol, benzodiazepines).

Cardiovascular and Hypertensive Effects

o Cardiovascular arrhythmias or hypertension can occur when sympathomimetic drugs are given with TCAs. o Interactants to avoid include norepinephrine, dopamine, ephedrine, and phenylpropanolamine.

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Interactions
Cardiovascular (continuation)
o Severe MAOI/TCA reactions, includes high fever, seizures, and a fatal hypertensive crisis, can occur if combined. MAOIs are not usually prescribed unless TCAs have failed.

Additive Anticholinergic Effects

o Additive anticholinergic effects can occur when TCAs are given with other anticholinergic drugs, including antipsychotics, antiparkinsonian drugs, and antihistamines. Older adult patients are especially susceptible.
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Nursing Implication
Therapeutic versus toxic blood levels Use during pregnancy Use in older adults Side effects Interactions Teaching patients

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Tricyclic Antidepressants
Amitriptyline Amoxapine (Asendin) Desipramine Imipramine Nortriptyline

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Monoamine Oxidase Inhibitors

Pharmacologic Effects
o Blocks monoamine oxidase, a major enzyme involved in the metabolic decomposition and inactivation of norepinephrine, serotonin, and dopamine.

Absorption, Distribution, and Administration

o Well absorbed from the GI tract and are given PO. o Metabolized in the liver. o MAOIs do not present the same age-related risks associated with other drugs.

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Monoamine Oxidase Inhibitors

Side Effects Causes CNS, cardiovascular, and anticholinergic side effects. Serious life-threatening reactions can occur when irreversible MAOIs interact with certain drugs or foods. Increases the availability of biogenic amines in the brain; CNS hyperstimulation might occur.

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Monoamine Oxidase Inhibitors

Drug-Drug Interaction
o Those that cause hypertension o Those that cause severe anticholinergic responses o Those that cause profound CNS depression

Food-Drug Interaction
o Tyramine-rich foods

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Nursing Implication
Therapeutic versus toxic drug levels
o Cheeking and hoarding

Use in pregnancy Use in older adults Side effects Indications and contraindications Teaching patients

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