As the name suggests, antidepressants are used to treat mood disorders, (and as the name implies) specifically, depressive disorders. Mood disorders are psychiatric disorders characterized by periods of depression, sometimes alternating with periods of elevated mood. Depression is a condition that causes persistent feelings of sadness and loss of interest, as well as physical symptoms. Common symptoms of depression include feelings of sadness or emptiness; loss of interest in daily activities; weight loss or weight gain (unintentional); difficulty with thinking and concentration; tearfulness; and feelings of worthlessness, sometimes with thoughts of death or suicide. Antidepressant medications are used for moderate to severe depression, but they can also be helpful with milder depression, which is sometimes called dysthymia. Dysthymia is a form of depression characterized by a lack of enjoyment/pleasure in life that continues for at least two years. It differs from clinical depression in the severity of the symptoms. while dysthymia usually does not prevent a person from functioning, it prevents full enjoyment of life. A person who suffers from a major depressive disorder must either have a depressed mood or a loss of interest or pleasure in daily activities consistently for at least a two-week period. This mood must represent a change from the person’s normal mood and impair his or her daily functioning. Single-episode depression is when something happens—your partner leaves you, you lose your job, your parent dies—and you experience a natural sadness and temporary depression. It’s a transitory reaction to an external event. Depending on the severity of the depressive episode, even if it is in reaction to a specific event and likely to be time-limited, it may still be helpful to put the patient on antidepressants on a temporary basis. Chronic depression is depression that doesn’t go away. It is an ongoing endogenous, or internal, condition, requiring antidepressant medication for an extended period of time, perhaps years, in order to improve the person’s ability to function. The first generation of antidepressant medications was the monoamine oxidase (MAO) inhibitors. These were followed by tricyclic antidepressants. The antidepressants used currently are primarily the SSRIs (selective serotonin reuptake inhibitors) and the so-called “dual-action” antidepressants—the SNRIs (serotonin-norepinephrine reuptake inhibitors). Monoamine oxidase is the enzyme that breaks down amines (a type of organic compound) in the brain. In the 1950s, researchers were looking for a treatment for tuberculosis and noticed that the experimental medication they were using elevated the mood of the patients in the test study. These patients became more active and more sociable, leading the researchers to conclude, “Hey, we’ve got something here—maybe we can develop these as mood-lifting pills.” MAO inhibitors are thought to work by increasing the level of certain neurotransmitters in the brain (since they are not being broken down or metabolized by the monoamine oxidase enzyme). These medications were used in the late 1950s but for the most part were discontinued in the early 1960s after they were linked to a number of deaths. when patients taking MAOIs ate certain foods, it caused severe hypertension, dizziness, and chest pain. It’s rare to see anybody on MAOIs anymore, though occasionally they are used for treatment-resistant patients. The second generation of antidepressants was the tricyclics, and these are still prescribed from time to time. Tricyclic antidepressants (TCAs) act as agonist catecholamines. Catecholamines are excitatory chemicals (amines) in your brain. TCAs block the absorption (reuptake) of the neurotransmitters serotonin and norepinephrine, making more of these chemicals available in the brain, boosting mood. TCAs do have a significant side-effect profile. Common side effects can include dry mouth, dry nose, blurry vision, lowered gastrointestinal motility or constipation, urinary retention, cognitive and/or memory impairment, and increased body temperature. Less frequent side effects can involve drowsiness, anxiety, emotional blunting (apathy/ anhedonia), confusion, restlessness, dizziness, hypersensitivity, changes in appetite and weight, sweating, sexual dysfunction, muscle twitches, weakness, nausea and vomiting, hypotension, and tachycardia. Besides these usual and potential side effects, the primary problem with these older drugs, like amitriptyline (Tryptomer, elavil), clomipramine (Anafranil), imipramine (Tofranil, Janimine, Praminil), and nortriptyline (Pamelor, Aventyl, Norpress) is the possibility of death by overdose due to cardiovascular and neurological toxicity. TCAs have demonstrated efficacy in the treatment of some forms of chronic pain, particularly neuralgia or neuropathic pain and fibromyalgia, and are sometimes used for that purpose. Currently the most prescribed antidepressants are the newer-generation medications. Selective serotonin reuptake inhibitors (SSRIs) first came on the market in the late 1980s and early 1990s. SSRIs work by selectively blocking the reuptake of serotonin in the synapses between neurons. Changing the balance of serotonin seems to help brain cells send and receive chemical messages, which in turn boosts mood. SSRIs are called selective because they seem to primarily affect serotonin, not other neurotransmitters. Actually, SSRIs are no more effective than tricyclic antidepressants, but they’re safer and better because they have fewer side effects. That notwithstanding, the side effects of SSRIs can include nausea, dry mouth, headache, diarrhea, nervousness, agitation or restlessness, reduced sexual desire or difficulty reaching orgasm, inability to maintain an erection (erectile dysfunction), weight gain, drowsiness, and insomnia. These side effects are most acute during the first one to four weeks while the body adapts to the drug (with the exception of sexual side effects, which tend to occur later in treatment). It often takes six to eight weeks for SSRIs to achieve their full therapeutic potential. The first SSRI to hit the market was fluoxetine (Prozac, Sarafem). Prozac was followed by paroxetine (Paxil, Paxil CR, Pexeva), sertraline (Zoloft), fluvoxamine (Luvox, Fevarin, Faverin, Dumyrox, Favoxil, Movox, Floxyfral), escitalopram (Lexapro), and citalopram (Celexa). Even more recent than the SSRIs are the serotonin-norepinephrine reuptake inhibitors (SNRIs). In addition to serotonin, SNRIs—sometimes called “dual-action” antidepressants—act upon, and increase (by blocking reuptake), the levels of another neurotransmitter known to play an important role in mood regulation: norepinephrine. SNRIs, which include duloxetine (Cymbalta), venlafaxine (effexor, effexor xR), and desvenlafaxine (Pristiq), and SSRIs generally have similar side effects. Interestingly, these medications have little effect on “normal” people but seem to be fairly effective in depressed people. SSRIs and SNRIs are also sometimes prescribed for anxiety disorders. But depending upon the individual taking these medications, there may be paradoxical reactions wherein some patients experience agitation, restlessness, or anxiety. Another newer antidepressant that you may hear about from time to time is wellbutrin (generic name is bupropion). This is an atypical antidepressant that seems to work by inhibiting norepinephrine-dopamine reuptake. Bupropion is one of few antidepressants that do not cause sexual dysfunction. In fact, some psychiatrists prescribe it as a treatment for SSRI-induced sexual dysfunction; some physicians may switch patients with SSRI-induced sexual dysfunction to bupropion, while others may augment current SSRI/SNRI medication with bupropion. However, we have to be careful in patients who have a seizure history because it can lower the seizure threshold. Bupropion is also used as an anti-smoking medication under the brand name Zyban. The GlaxoSmithKline pharmaceutical company discovered that when wellbutrin was administered to depressed people who also smoked cigarettes, many of them stopped smoking. So they applied to the FDA for it to be approved as a smoking cessation medication (it was), and were able to market one medication for two very different uses. When you have clients who are prescribed antidepressants, it’s important to make sure they are aware that the meds have to be taken for a period of time before they start working. Although their prescribing doctor already informed them of this, you have to remind your clients that it may take weeks, or perhaps a month or two, before they begin to experience relief from their depressive symptoms. Sometimes people ask me how long they should stay on their medications. If they tell me that they’re feeling better, I tell them to stay on it for at least six months and then after that, if they want to, they can start tapering it and see if the depression comes back. If it comes back, then they may need to be on it longer. Even when they are not getting desirable results, it is generally not advisable for people on antidepressants to suddenly stop taking them without consulting their prescribing physician. With many psychiatric medications, and particularly the SSRIs like Prozac and Paxil, we sometimes see a “discontinuation syndrome.” Antidepressant discontinuation syndrome occurs in approximately 20 percent of patients after abrupt discontinuation of an antidepressant medication that has been taken for at least six weeks. Typical symptoms of antidepressant discontinuation syndrome include flu-like symptoms, insomnia, nausea, imbalance, sensory disturbances, and hyperarousal. These symptoms usually are mild and last one to a few weeks, which means if a person stops their Paxil suddenly because they ran out and decided “who needs this stuff, I don’t want to be on it anymore,” they’ll go through a type of withdrawal. For people with severe depression who are unresponsive to antidepressants, electroconvulsive therapy (eCT) may be helpful. The mention of eCT can conjure up unpleasant and frightening images that are based on the way it was administered decades ago. However, modern eCT is altogether different—it is safe and can be very effective, and there are no real adverse effects except for some memory loss. This blog post is an excerpt from The therapist’s Guide to Addiction Medicine – A Handbook for Addiction Counselors and Therapists – by Barry Solof, MD, FASAM; Published by Central Recovery Press (CRP).