Antidepressants for Major Depression - SSRIs

Rashmi Nemade, Ph.D., Natalie Staats Reiss, Ph.D., and Mark Dombeck, Ph.D.

Antidepressants 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.

Selective Serotonin Reuptake Inhibitors (SSRIs)

In healthy brain synapses, one neuron communicates with another via neurotransmitters that traverse across a small gap between them known as a synapse. Neurotransmitter molecules activate receptor molecules on the post-synaptic neuron surface, causing the post-synaptic neuron to become active. Once activation has occurred, the post-synaptic neuron releases the neurotransmitter molecules back into the synapse where they are taken back up by the pre-synaptic neuron for reuse in a future message.

The Selective Serotonin Reuptake Inhibitors, or SSRIs for short, are a popular family of antidepressant drugs frequently prescribed today. Selective serotonin reuptake inhibitors are thought to work by slowing down the reuptake of neurotransmitter molecules (in this case specifically serotonin molecules) by pre-synaptic neurons. Because serotonin reuptake is prevented, serotonin molecules end up staying in the synapse longer than they normally would, and get more of a chance to activate the post-synaptic neuron. There are several types of serotonin receptors, and some medications work on specific receptors better than others.

Fluoxetine (Prozac) is used for the treatment of major depressive disorder, obsessive compulsive disorder (OCD; a person experiences obsessions, or repetitive uncontrollable thoughts, and compulsions, or repetitive uncontrollable behaviors such as repeatedly washing one's hands), bulimia nervosa (an eating disorder characterized by binges and vomiting), and panic disorder (an anxiety disorder accompanied by feelings of terror that strike suddenly and repeatedly with no warning) with or without agoraphobia (anxiety about being in situations from which escape might be difficult or embarrassing). Prozac used for the treatment of premenstrual dysphoric disorder (mood changes associated with the menstrual cycle), is packaged as Sarafem (fluoxetine hydrochloride).

Side effects of Prozac include: chest pain, chills, hemorrhage (bleeding or abnormal flow of blood), hypertension (high blood pressure, palpitation (irregular and/or forceful beating of the heart), increased appetite, nausea, vomiting, weight gain, agitation, amnesia (impaired memory), confusion, emotional lability (rapidly changing mood), sleep problems, and an increased need to urinate.

Prozac should not be used in combination with monoamine oxidase inhibitors (MAOIs), which are another type of antidepressant medication, or thioridazine (a medication used to treat psychotic disorders, severe depression or anxiety, or severe behavior problems in children). In addition, people should be careful about using Prozac in combination with NSAIDs (pain medication such as ibuprofen), aspirin or other drugs that affect blood coagulation since this increases the risk of bleeding. There is also a risk of developing Serotonin Syndrome, a cluster of uncomfortable and potentially dangerous side effects including agitation, hallucinations, coma, chills, headache, fluctuations in blood pressure, rapid heart beat, raised body temperature, nausea, vomiting, diarrhea, profuse sweating, confusion, and restlessness. As a result, people taking Prozac should avoid taking other medications that affect serotonin such as triptans (used for treating migraines), tryptophan (5-HTP, a dietary supplement used for depression), linezolid (an antibiotic used to treat infections), tramadol (used for pain), St. John's Wort (an herb used for depression), or other SSRIs/SNRIs.

Sertaline (Zoloft) is used for treating major depressive disorder, OCD, panic disorder, posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder, and social anxiety disorder (fear of social or performance situations involving exposure to unfamiliar people or possible scrutiny by others). Side effects of Zoloft include: impotence (a consistent inability to sustain or achieve an erection), heart palpitations (irregular and/or forceful beating of the heart), chest pain, hypertonia (increased muscle tightness), increased appetite, back pain, myalgia (muscle pain), yawning, male and female sexual dysfunction, rhinitis (irritation of the nose), and tinnitus (ringing in the ears). As with Prozac, Zoloft should not be used with MAOIs or thioridazine. In addition, people taking Zoloft should not take pimozide (Orap), a medication used for the treatment of Tourette's Disorder (characterized by motor and oral tics). Zoloft may also affect a person's lithium levels (used for the treatment of bipolar disorder), so close monitoring may be necessary. There is also a risk of Serontonin Syndrome when taking Zoloft.

Paroxetine (Paxil) is used for the treatment of major depressive disorder, social anxiety disorder, OCD, panic disorder, generalized anxiety disorder (GAD; an exaggerated or unfounded state of worry and anxiety, often about such everyday matters as health, money, family, or work ), and PTSD. Side effects include: asthenia (lack of energy), sweating, nausea, decreased appetite, sleepiness, dizziness, insomnia, tremor, nervousness, impotence, problems with ejaculation and other male genital disorders, dry mouth, and constipation. The same warnings listed above apply, people taking Paxil should avoid MAOIs, thioridazine, and pimozide. In addition, the same potential for Serotonin Syndrome exists when taking Paxil.

Citalopram (Celexa) is used for the treatment of major depressive disorder. Side effects include: tachychardia (rapid heart rate), postural hypotension (a drop in blood pressure due to a change in body position), hypotension (low blood pressure), paresthesia (abnormal skin sensensations such as numbness, tingling, pricking, or burning), migraine, increased flatulence, weight gain, weight loss, impaired concentration, amnesia (impaired memory), increased depressive symptoms, increased appetite, suicide attempts, confusion, amenorrhea (cessation of a woman's period), coughing, blurry vision, rash, itching, and increased need to urinate. As with the above medications, people taking Celexa should avoid MAOIs, thioridazine, pimozide, NSAIDs, aspirin, or other drugs that affect coagulation; and watch for signs of Serotonin Syndrome.

Escitalopram (Lexapro) is used for the treatment of major depressive disorder and GAD. Side effects include: heart palpations, hypertension (high blood pressure), light-headedness, migraine, heartburn, abdominal cramps, gastroenteritis (inflammation or infection of the stomach or intestines), limb/muscle/joint pain, fever, hot flushes, chest pain, weight gain, increased appetite, lethargy, irritability, impaired concentration, bronchitis (inflammation and swelling of the airways of the lung) nasal/sinus congestion, coughing, sinus headache, rash, blurry vision, tinnitus (ringing in the ears), increased need to urinate, and urinary tract infections. As with the above medications, people taking Lexapro should avoid MAOIs, thioridazine, pimozide, NSAIDs, aspirin, or other drugs that affect coagulation; and watch for signs of Serotonin Syndrome. For more information on Lexapro, please see our sponsored topic center.

Practically speaking, SSRIs are easy to use. They are taken only once a day, which increases the likelihood that people will comply with treatment and take their medications. They are available in pill form and sometimes as liquids. The pill form is most often prescribed. As with any medication, the risk of overdose is always a possibility. Overdose can cause vomiting, seizures, and even death, particularly when people mix SSRI's with other drugs or with alcohol. In general, reports of overdose with SSRIs are rare, and SSRIs are considered fairly safe medications. To reduce the risk for overdose, your physician may write you a prescription for a small quantity of medication at a time, which will require that you refill your prescription frequently.

Increasing a depressed person's amount of serotonin in their brain does not always improve their mood. Some depressed people 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 newer antidepressants that also target other neurotransmitters that impact mood.

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