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The Reuptake Inhibitors
When choosing a medication for depression, most physicians first start with selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) because they tend to carry fewer serious side effects than older medications.
SSRIs, are usually the first choice. These include fluoxetine, sertraline, paroxetine, escitalopram, and citralopram. They work by helping the brain regulate serotonin, a chemical thought to be responsible for changes in mood. SSRIs are effective at treating moderate to severe depression, and typically cause fewer side effects than other types of medication for depression. Common side effects include nausea, headache, agitation, dry mouth, drowsiness, and weight gain. SSRIs are available in controlled-release and extended-release form.
SNRIs work by inhibiting the reabsorption of both serotonin and norepinephrine in the brain, making both chemicals more widely available, which in turn helps regulate moods. Norepinephrine works as both a hormone and a neurotransmitter. As a neurotransmitter, it helps pass nerve impulses from neuron to neuron. Altering the balance of the two chemicals aids the brain cells in sending and receiving messages. SNRIs include duloxetine, venlafaxine, and desvenlafaxine. They come in immediate-release form requiring up to three doses per day, or extended-release form requiring a single dose each day. Side effects vary depending on the type of medication, and may include nausea, dizziness, insomnia, constipation, heart palpitation, and changes in appetite. Blurred vision and muscle weakness can also occur in some patients.
Both SSRIs and SNRIs cause sexual side effects, including erectile dysfunction and lowered libido, in over half the patients that take them, according to the Mayo Clinic.
They may also increase the risk of suicidal thoughts or behavior in children, adolescents, and young adults up to age 24. Patients in these age groups require careful monitoring, especially when first starting the medication or changing dosages.
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Atypical antidepressants are chemically different from other antidepressants.
Bupropion, the only FDA-approved norepinephrine and dopamine reuptake inhibitor, is relatively new to the antidepressant scene. Like SSRIs and SNRIs, bupropion works by inhibiting the reuptake and increasing the availability of chemicals thought to play a major role in mood regulation. Side effects are similar to SNRIs, with the addition of a risk of increased blood pressure and tinnitus. Unlike other types of reuptake inhibitors, bupropion doesn’t cause sexual side effects or weight gain. It is a good choice for those suffering from low energy and those trying to quit smoking. It is not recommended for those with seizure disorders or a history of eating disorders.
Mirtazapine is another atypical medication, used to treat major depressive disorder. Because the medication can cause sedation, it is typically taken at night. Like other antidepressants, mirtazapine works by balancing brain chemicals responsible for mood. Common reactions include increased appetite, weight gain, strange thoughts or dreams, increased urination, and sun sensitivity. Mirtazapine can also increase cholesterol levels, so additional monitoring may be required for those with a history of high cholesterol or hardening of the arteries.
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Tricyclic and tetracyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are two of the oldest types of medication for depression. Although they are still highly effective, they are often used as a last resort because of the risk of severe side effects. TCAs approved by the FDA for treatment of depression include amitriptyline, desipramine, imipramine, and amoxapine. TCAs work similarly to SNRIs by inhibiting the reuptake of serotonin and norepinephrine. However, they also tend to block certain receptors, include muscle, histamine, and alpha adrenergic receptors. These blockades cause the majority of the unfavorable side effects associated with TCAs. Side effects include blurred vision, increased heart rate, sedation, weight gain, sun sensitivity, and confusion.
MAOIs were the first antipressants developed, and although they are still effective, they are usually used as the absolute last resort because of the potentially serious side effects and the required lifestyle changes. Like their successors, they work by inhibiting reabsorption of mood-regulating chemicals. However, unlike the selective reuptake inhibitors, MAOIs inhibit all monoamines in the brain, including the enzyme that breaks down tyramine, an amino acid that helps to regulate blood pressure. Too much tyramine in the body can cause dangerously high blood pressure. Those taking MAOIs must avoid certain foods that contain tyramine, including many types of cheese, cured meats, soy sauce, beer and wine. MAOIs also dangerously interact with many medications, such as other antidepressants, pain medications, decongestants, and herbal supplements. Weight gain, muscle aches, nervousness, and a tingling sensation in the skin can also occur while taking MAOIs.
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Note Regarding All Antidepressants
Choosing the right medication for depression often requires trying several different types before finding the one that works best, and careful monitoring is required while finding the right fit. Never stop taking an antidepressant abruptly without contacting a physician, as this can cause withdrawal symptoms.
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Mayo Clinic: Depression- Treatments and Drugs
PubMed Health: Bupropion
Pharmacology Corner: Differences Between TCAs and SNRIs