The selective serotonin reuptake inhibitors (SSRIs) are likely the most widely prescribed antidepressants in the United States and, probably, the world. They have revolutionized the treatment of depression because of their improved safety and tolerability over the previously used tricyclic antidepressants and monoamine oxidase inhibitors, which could be lethal in overdose. In addition, the cardiac toxicity and problematic anticholinergic side effects are absent from the SSRIs. Rarely could patients tolerate using the older antidepressants for any significant length of time because of their side effects, and thus the result would be reemergence of their symptom presentations. The SSRIs, on the other hand, could be used in long-term treatment, and adherence was much improved. Another advantage of the SSRIs is their broad therapeutic profile. Their use extends well beyond their antidepressant actions. For instance, they have proven efficacy in anxiety spectrum disorders such as generalized anxiety disorder, panic disorder, social phobia, specific phobias, obsessive-compulsive disorder, posttraumatic stress disorder, eating disorders, and a host of other disorders for which there are no pharmacologic indications for any other category of medication. The SSRIs have also been used in a multitude of nonpsychiatric disorders such as migraine and pain syndromes such as fibromyalgia and neuropathic pain.
Before the development of the SSRIs, the antidepressants used most were the tricyclic antidepressants such as amitriptyline and imipramine. These were similar to the SSRIs but also targeted receptors that caused significant side effects. These were unofficially known as the "dirty antidepressants" because of their generally intolerable side effects. When the SSRIs came along, they became unofficially known as the "clean antidepressants" because they did not have a high affinity for the receptors that caused the intolerable side effects.
Understanding the pharmacodynamics of these medications requires an understanding of the psychopathology. One theory of depression (although there are several) states that there is a decrease of serotonin available at the synapse and, as a result, fewer receptors are stimulated and depression occurs. We now know that the presynaptic neuron secretes serotonin into the synapse where it travels to the postsynaptic neuron and stimulates the receptor. In health, when the serotonin molecule falls off the receptor, it is "sucked" back into the presynaptic neuron via an active transport pump, and once inside the neuron, it is repackaged for use at a later time. In the event that there is not enough serotonin produced or the reuptake pump is working harder and faster than it should, the SSRI blocks the pump so the serotonin builds up at the synapse, and eventually, there is enough to stimulate the receptors and diminish the depressive symptoms.
The current slate of SSRIs includes fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram. Because of their relatively nontoxic effects, the SSRIs are used in the treatment of many disorders. Indications for the use of an SSRI include the following and do not necessarily apply to all the SSRIs. Information on the indications for specific SSRIs can be found at other sources such as the Physicians' Desk Reference or the manufacturer's package insert or Web site. The indications include major depressive disorder, bulimia nervosa, obsessive-compulsive disorder, panic disorder, social anxiety disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and generalized anxiety disorder. The SSRIs have also been used "off-label" (not an approved indication) such as in dysthymic disorder, binge eating disorder, dementia, borderline personality disorder, chronic fatigue syndrome, body dysmorphic disorder, pervasive developmental disorder, trichotillomania, premature ejaculation, and hot flashes in women in menopause, to name a few.
The SSRIs have been associated with increased suicidal ideation, hostility, and psychomotor agitation in clinical trials involving children, adolescents, and young adults up to 24 years old. This effect was not seen in those aged 24-65 years. All patients should be monitored for worsening of depression and suicidal thinking.
Pharmacokinetically, the SSRIs are absorbed relatively slowly but completely and undergo little first-pass effect. However, they are highly bound to plasma protein and will displace other drugs from protein binding. They are metabolized primarily by the liver, and clearance of all SSRIs is reduced in patients with liver cirrhosis. Thus, in hepatic compromised patients, their use should be monitored closely or, ideally, they should be not used.
The most common side effects include central nervous system, gastrointestinal, and sexual side effects. Headaches are common and can be treated with nonsteroidal anti-inflammatory drugs or acetaminophen, as needed. The SSRIs can cause activation or sedation. If sedation occurs, give the medication at bedtime. Activation, excitement, impulse dyscontrol, anxiety, agitation, and restlessness occur more frequently at higher doses and usually earlier rather than later in treatment. Because most serotonin and its receptors are found in the gut, an increase in serotonin may cause nausea, vomiting, diarrhea, and bloating. These symptoms are usually transient and will decrease with time as the receptors in the gut become desensitized to continuous stimulation. An interesting initial effect is anorexia and weight loss-probably as a result of the gastrointestinal side effects. However, these symptoms generally abate, and often, there is weight gain. Sexual side effects include decreased libido, impotence, ejaculatory disturbances, anorgasmia, and delayed orgasm, which unfortunately occur relatively frequently. Some of the medications used to neutralize these effects include sildenafil, amantadine, buspirone, and bupropion. Hypersensitivity reactions are rare, and if they occur, the medication should be stopped.
Abrupt discontinuation of high doses of the SSRI may cause discontinuation syndrome consisting of somatic symptoms such as dizziness, lethargy, nausea, vomiting, diarrhea, headache, fever, sweating, chills, malaise, insomnia, vivid dreams, myalgia, and paresthesias and psychologic symptoms such as anxiety, agitation, crying, irritability, and slowed thinking. These symptoms can be quite disturbing and distracting to the patient, and therefore these medications should be tapered gradually after prolonged use. The general rule is 25% per week and monitor for recurrence of depressive symptoms. The exception to this rule is fluoxetine because of its prolonged half-life. However, fluoxetine should still be tapered but can be done more quickly.
As nurses, we understand that depression is caused by both internal and external stressors and the medications only address the internal (neurobiologic) issues and not the external (environmental) issues, and so psychotherapy and education are of paramount importance in the treatment of depression. At every session, we should also monitor both side effects and therapeutic effects and document accordingly. Educating ourselves and our patients on the use of SSRIs-both the benefits and the risks-is most important. No matter what your role in nursing is, we are all held to a higher standard in ensuring our patients are receiving optimal, evidence-based, and safe care.