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- What is an antidepressant medication?
- How do antidepressants work?
- How do selective serotonin reuptake inhibitors (SSRIs) work?
- What are the side effects of SSRIs?
- What are examples of SSRIs?
- How do serotonin norepinephrine reuptake inhibitors (SNRIs)? work
- What are the side effects and drug interactions for SNRIs?
- What are examples of SNRIs?
- What are examples and side effects of tricyclic antidepressant (TCA) medications?
- What are examples and side effects of monoamine oxidase inhibitor (MAOI) medications?
- What other antidepressants are available?
What is an antidepressant medication?
Depression is a serious condition that often can be effectively treated with available therapies. Many antidepressants have been developed over the years. The newer classes of antidepressants are better tolerated and associated with fewer drug interactions than the older class of antidepressants. Side effects and drug interactions are barriers to successful treatment. Some side effects of antidepressants resolve with continued use while other side effects can be managed by dose reduction or adding other therapies. Appropriate management of side effects and avoidance of drugs that may interact with antidepressants may improve the success of antidepressant therapy.
This article discusses side effects and potential drug interactions of the major antidepressant classes.
How do antidepressants work?
Antidepressants are the most prescribed drug for depression. The exact mechanism of action of antidepressants is unknown.
- The prevailing theory is that antidepressants increase the
concentration of one or more brain chemicals (neurotransmitters) that nerves in the brain use to communicate with one
- The neurotransmitters affected by antidepressants are norepinephrine, serotonin, and dopamine.
- The different classes of antidepressants differ in the neurotransmitters they affect. This determines some of their side effects and potential drug interactions.
- All available antidepressants are effective, and for most cases of depression there is no good evidence that any antidepressant is more effective than another.
- Side effects, potential drug interactions, and therapy compliance are major factors that influence a doctor's selection of antidepressants for a patient.
Quick GuidePhysical Symptoms of Depression in Pictures
How do selective serotonin reuptake inhibitors (SSRIs) work?
SSRIs are the most widely used class of antidepressants. They work by increasing the level of serotonin in the brain. Unlike MAOIs and TCAs, SSRIs do not significantly affect norepinephrine levels in the brain. SSRIs also have fewer and milder side effects, fewer drug interactions, and are much less likely to be associated with suicide than TCAs.
What are the side effects of SSRIs?
- Headaches: SSRIs cause headaches and dose-related nausea, vomiting, and diarrhea that improve with continued treatment.
- Insomnia, restlessness, agitation: Insomnia, restlessness, and agitation-which decrease over time-also are associated with SSRIs. Insomnia can be treated with low dose (50-100 mg) trazodone (Desyrel) at bedtime and agitation may be managed by reducing the SSRI dose or treating with anti-anxiety drugs.
- Sexual dysfunction: SSRIs also are associated with sexual dysfunction. Symptoms of sexual dysfunction in men may be treated with sildenafil (Viagra), yohimbine (Pausinystalia yohimbe), amantadine (Symmetrel), cyproheptadine, or neostigmine (Prostigmin).
- Weight gain or loss: Over time, weight loss or weight gain has been associated with SSRIs. Patients may experience weight loss initially but quickly regain weight.
What drugs interact with SSRIs?
- Confusion, high blood pressure, tremor, hyperactivity, coma, and death may occur when SSRIs are combined with other drugs that increase brain serotonin levels, for example, MAOIs, TCAs, sumatriptan (Imitrex), linezolid (Zyvox), St John's Wort, tramadol (Ultram), and meperidine (Demerol).
- The risk of gastrointestinal bleeding may be increased when SSRIs are combined with nonsteroidal anti-inflammatory drugs (NSAIDs).
- SSRIs may increase the effect of the blood thinner warfarin (Coumadin, Jantoven), leading to excessive bleeding. Therefore, warfarin therapy, and patients taking NSAIDs should be monitored more frequently with PT/INR testing in individuals who also are taking SSRIs.
What are examples of SSRIs?
How do serotonin norepinephrine reuptake inhibitors (SNRIs)? work
SNRIs are the newest class of antidepressants. SNRIs work by increasing the levels of serotonin and norepinephrine that are active in the brain. Serotonin and norepinephrine are produced by nerves and released into the surrounding tissues where they can attach to nearby receptors on other nerves, thereby stimulating the other nerves. The released serotonin and norepinephrine then are taken up and released again by the nerves that produce them. SNRIs block the uptake ("reuptake") of the serotonin and norepinephrine so that more of the serotonin and norepinephrine are free in the tissues surrounding the nerves.
Quick GuidePhysical Symptoms of Depression in Pictures
What are the side effects and drug interactions for SNRIs?
Drug interactions and side effects associated with SNRIs are similar to those seen with SSRIs.
SNRIs may increase blood pressure, especially at high doses. High blood pressure caused by SNRIs may be managed by reducing the dose of the SNRI.
What are examples and side effects of tricyclic antidepressant (TCA) medications?name="tricyclic_antidepressants_tcas">
What are examples and side effects of tricyclic antidepressant (TCA) medications?
- TCAs have been in use since the 1950s when imipramine (Tofranil) was shown to be effective for treating depression.
- TCAs primarily work by increasing the level of norepinephrine in the brain and to a lesser extent serotonin levels.
- Some TCAs also are antihistamines (block the action of histamine) or anticholinergic (block the action of acetylcholine, a neurotransmitter), and these additional actions allow for uses of TCAs other than for treating depression as well as additional side effects.
What are the side effects of tricyclic antidepressants (TCA) medications?
Serious side effects and adverse events of tricyclic antidepressants include:
- TCAs are associated with a number of cardiovascular (heart and blood vessels) effects such as orthostatic hypotension and abnormal heart rates and rhythms. Orthostatic hypotension may lead to dizziness, falls, and fractures. Orthostatic hypotension may be managed by reducing or discontinuing the TCA dose, increasing salt intake, or treatment with steroids.
- If abnormal heart rhythms develop, TCAs should be discontinued. TCAs are not a good choice for patients with cardiovascular conditions.
- TCAs have anticholinergic effects which manifest as dry mouth, constipation, urinary hesitation, sexual dysfunction, increased heart rate, and visual disturbance. Desipramine (Norpramin) and nortriptyline (Pamelor) cause less anticholinergic effects than other TCAs.
- TCAs should be avoided by individuals with prostatic hypertrophy, cognitive impairment, or narrow-angle glaucoma because drugs with anticholinergic side effects can worsen symptoms of these conditions.
Some side effects and treatments of tricyclic antidepressants include:
- Dry mouth relief: Sugarless gum or candy, or pilocarpine (Salagen) oral rinse may alleviate dry mouth.
- Constipation: Constipation may be relieved by bulk laxatives and increased drinking hydrating fluids.
- Urinary retention: Urinary hesitation may be treated with bethanechol (Urecholine).
- Visual disturbances: Visual disturbances may be treated with pilocarpine eye drops.
- Sexual dysfunction: Erectile dysfunction (ED, impotence) may be managed with sidenafil (Viagra), reducing the TCA dose or discontinuing the TCA. Yohimbine, ginkgo, bethanechol, and neostigmine have also been used for managing TCA induced sexual dysfunction in some patients.
More serious side effects include:
- TCAs also cause sedation. Amitriptyline (Elavil, Endep), doxepin (Sinequan), and trimipramine (Surmontil) are more sedating than amoxapine and desipramine (Norpramin). Sedation may improve after a few weeks of treatment. Sedating TCAs may be beneficial for depressed patients who have insomnia.
- Dose dependent and reversible weight gain may occur during TCA treatment. Amitriptyline (Elavil, Endep) causes weight gain more often than desipramine (Norpramin).
What drugs interact with TCAs?
- TCAs may inhibit the antihypertensive effect of clonidine (Catapres). Therefore, combining TCAs with clonidine may lead to dangerous elevations in blood pressure.
- TCAs may affect the heart's electrical conduction system. Combining TCAs with drugs that also affect the heart's conduction system (for example, disopyramide [Norpace], pimozide [Orap], procainamide [Pronestyl, Procan SR, Procanbid]) may increase the frequency and severity of an abnormal heart rate and rhythm.
- Combining TCAs with carbamazepine (Tegretol) may result in lower TCA blood levels because carbamazepine increases the break down of TCAs, potentially reducing their effect.
- TCAs may increase the blood pressure elevating effect of epinephrine, norepinephrine, dopamine, phenylephrine, and dobutamine.
- Cimetidine (Tagamet) may reduce the breakdown of some TCAs, for example, amitriptyline (Elavil, Endep), increasing the level of the TCA in the body and potentially leading to increased side effects. As mentioned previously, TCAs should not be combined with MAOIs.
What are examples of TCAs?
- amitriptyline (Elavil and Endep are discontinued brands in the US)
- clomipramine (Anafranil)
- desipramine (Norpramin)
- doxepin (Sinequan and Adapin are discontinued brands in the US)
- imipramine (Tofranil)
- nortriptyline (Pamelor; Aventyl is a discontinued brand in the US)
- protriptyline (Vivactil)
- trimipramine (Surmontil)
What are examples and side effects of monoamine oxidase inhibitor (MAOI) medications?
MAOIs were the first class of antidepressants to be developed. They fell out of favor because of concerns about interactions with certain foods and numerous drug interactions. MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by inhibiting an enzyme called monoamine oxidase. Monoamine oxidase breaks down norepinephrine, serotonin, and dopamine. When monoamine oxidase is inhibited, norepinephrine, serotonin, and dopamine are not broken down, increasing the concentration of all three neurotransmitters in the brain.
Monoamine oxidase also breaks down tyramine, a chemical present in aged cheese, wines, and other aged foods. Since MAOIs inhibit monoamine oxidase they decrease the breakdown of tyramine from ingested food, increasing the level of tyramine in the body. Excessive tyramine can elevate blood pressure and cause a hypertensive crisis. Patients treated with MAOIs should adhere to recommended dietary modifications that reduce the intake of tyramine. Interestingly, the 6 mg/24 hour dose of selegiline transdermal system (EMSAM, and MAO inhibitor) does not require dietary restrictions because at this dose EMSAM does not substantially inhibit tyramine. Higher selegiline transdermal system (EMSAM) doses require dietary restrictions.
What are the side effects of MAOIs?
- MAOIs are associated with headache and insomnia which may decrease with continued use. Headaches may require treatment with nonsteroidal anti-inflammatory drugs (for example, ibuprofen), and insomnia may require treatment with benzodiazepines (for example, diazepam [Valium]) or other drugs for insomnia.
- Because MAOIs stimulate the nervous system, they may be beneficial for depressed patients who over sleep or are fatigued.
- Hypertension may occur during therapy with MAOIs. Therefore, blood pressure should be monitored periodically during MAOI treatment. Hypertensive crisis may occur when MAOIs are combined with tyramine containing foods or drugs that constrict blood vessels.
Symptoms of hypertensive crises include
- heart palpitation,
- chest pain,
- increased or decreased heart rate,
- neck stiffness or soreness,
- sweating, and
- dilated pupils.
Other side effects and adverse events of MAOIs include:
- Bleeding in the brain also may occur. Patients should be aware of signs and symptoms of hypertensive crisis and should seek immediate medical treatment if these signs or symptoms are present. Hypertensive crisis may be managed with nitroprusside (Nitropress), labetalol (Normodyne, Trandate), or phentolamine.
- Orthostatic hypotension (feeling faint upon standing due to decreased blood flow to the brain) also occurs. Patients should rise slowly from a sitting position to reduce the effect of orthostatic hypotension. Orthostatic hypotension may be treated with steroids.
- Some patients may experience peripheral edema (swelling of the lower legs and ankles) which can be improved by wearing support stockings.
- MAOIs also are associated with sexual side effects such as decreased sexual drive, erectile dysfunction, difficulty ejaculating or reaching orgasm. Sexual side effects may diminish with time or a reduction in dose.
What drug interactions may occur with MAOIs?
MAOIs are associated with several significant drug interactions; limiting their usefulness in patients who are treated with multiple drugs. MAOIs interact with drugs that increase serotonin activity in the brain, increase norepinephrine, constrict blood vessels, or inhibit monoamine oxidase.
Drugs that increase serotonin in the brain include:
- selective serotonin reuptake inhibitors, for example, fluoxetine (Prozac), paroxetine (Paxil, Paxil CR, Pexeva), fluvoxamine (Luvox), and sertraline (Zoloft)
- serotonin norepinephrine reuptake inhibitors, for example, venlafaxine (Effexor) and desvenlafaxine (Pristiq)
- tricyclic antidepressants, for example, imipramine (Tofranil), desipramine (Norpramin), amitriptyline
- St. John's Wort
- tramadol (Ultram)
- fentanyl (Sublimaze, Duragesic)
- propoxyphene (Darvon)
- other MAOIs, for example, tranylcypromine (Parnate), phenelzine (Nardil), isocarboxazid (Marplan)
Combining MAOIs with drugs that increase serotonin may cause
- coma, and
Combining MAOIs with norepinephrine or drugs that constrict blood vessels (epinephrine, amphetamines, pseudoephedrine, ephedrine, phenylpropanolamine, and phenylephrine) may increase blood pressure to dangerous levels.
The antibiotic linezolid (Zyvox) and intravenous methylene blue should not be combined with MAOIs because they also inhibit monoamine oxidase.
MAOIs should be discontinued at least two weeks before administration of drugs that interact with MAOIs. Drugs that interact with MAOIs should be discontinued at least 1-2 weeks before administration of MAOIs. Because the effect of fluoxetine lasts for several weeks after discontinuation, MAOIs should not be initiated for at least five weeks after stopping fluoxetine.
What are examples of MAOIs?
- phenelzine (Nardil)
- tranylcypromine (Parnate)
- isocarboxazid (Marplan)
- selegiline transdermal system (EMSAM)
Quick GuidePhysical Symptoms of Depression in Pictures
What other antidepressants are available?
Reference: FDA Prescribing Information
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