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Antidepressants for Depressive Disorders

Rashmi Nemade, Ph.D., edited by Kathryn Patricelli, MA

Recall our earlier discussion of neurotransmitters, synapses and receptors? This may be a good point to review that information (by clicking here), as in the following sections we will be discussing how the various families of antidepressant medications are thought to affect these neuronal systems.

pill bottleSelective serotonin reuptake inhibitors (SSRIs). Doctors often start by prescribing an SSRI. These medications are safer and generally cause fewer bothersome side effects than other types of antidepressants. They are thought to work by slowing down the reuptake of serotonin neurotransmitter molecules by neurons that are found before the tiny gaps (synapses). Because serotonin reuptake is prevented, serotonin molecules end up staying in the gap longer than they normally would, and get more of a chance to activate the neuron found after the gap. There are several types of serotonin receptors, and some medications work on specific receptors better than others. SSRIs include fluoxetine (Prozac, Selfemra), paroxetine (Paxil, Pexeva), sertraline (Zoloft), citalopram (Celexa) and escitalopram (Lexapro). Increasing the amount serotonin in the brain of a person with depression does not always improve their depression. Some people with depression also need help increasing levels of additional neurotransmitters such as norepinephrine. Often, people who don't respond to SSRI's will receive a trial of other antidepressants that also target other neurotransmitters that impact mood.

Serotonin and norepinephrine reuptake inhibitors (SNRIs) affect serotonin, as well as norepinephrine and other neurotransmitter systems such as dopamine. SNRIs work like SSRIs in that they inhibit the reuptake of neurotransmitters at the junction between the transmitters. Examples of SNRI medications include duloxetine (Cymbalta), venlafaxine (Effexor XR), desvenlafaxine (Pristiq, Khedezla) and levomilnacipran (Fetzima).

Norepinephrine and dopamine reuptake inhibitors (NDRIs) work in the same way as the other neurotransmitter reuptake inhibitors, but target norepinephrine and dopamine. Bupropion (Wellbutrin, Aplenzin, Forfivo XL) falls into this category. It's one of the few antidepressants not frequently associated with sexual side effects.

Tricyclic antidepressants. Although these are the oldest antidepressants on the market, they are typically second or third choice treatments. Because of the long list of side effects associated with this family of medication, including weight gain, sedation, visual disturbances (e.g., problems focusing), anxiety, and sexual dysfunction, there is little interest in further research or development of TCAs. In addition, these medications are potentially toxic at high levels, making them a problem from an overdose perspective. Blood monitoring of medication levels is sometimes used to help ensure that helpful rather than toxic (harmful) blood levels are maintained. The tricyclic medications are mostly used today when other newer medications have failed. Some common TCAs are imipramine (Tofranil), nortriptyline (Pamelor), amitriptyline, doxepin, trimipramine (Surmontil), desipramine (Norpramin) and protriptyline (Vivactil).

Monoamine oxidase inhibitors (MAOIs) are enzymes that break down serotonin, norepinephrine, and dopamine. By preventing these enzymes from working, MAOI medications allow neurotransmitters to remain in the synaptic gap longer.  This gives them more opportunity to activate the post-synaptic neuron's receptors and create greater stimulation of the post-synaptic recipient neuron. Increasing someone's serotonin, norepinephrine, and/or dopamine levels tends to have an antidepressant effect. Using an MAOI requires a strict diet because of dangerous (or even deadly) interactions with foods, such as certain cheeses, pickles and wines.  It can also interact with some medications, including birth control pills, decongestants and certain herbal supplements. MAOIs, such as tranylcypromine (Parnate), phenelzine (Nardil) and isocarboxazid (Marplan) may be prescribed, often when other medications haven't worked, because they can have serious side effects. Selegiline (Emsam), a newer MAOI that you stick on your skin as a patch, may cause fewer side effects than other MAOIs. These medications cannot be combined with SSRIs.

Atypical antidepressants. These medications don't fit neatly into any of the other antidepressant categories. They include trazodone (Oleptro), mirtazapine (Remeron) and vortioxetine (Brintellix). These make a person very tired and are usually taken in the evening. A newer medication called vilazodone (Viibryd) is thought to have a low risk of sexual side effects.

Other antidepressants. There are many other substances used for their antidepressant effects such as lithium, Omega-3 fatty acids, stimulants, thyroid replacement therapies, and herbal remedies. There are also alternative medicines such as Traditional Chinese Medicine, Ayurveda, and Homeopathy that are used. However, more research is needed to understand and use these treatments effectively. These therapies are not without their own side effects and should always be used under the supervision of a doctor.

Other medications may be added to an antidepressant to enhance their effects. A doctor may recommend combining two antidepressants or medications such as mood stabilizers or antipsychotics. Anti-anxiety and stimulant medications might also be added for short-term use.

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