Selective serotonin reuptake inhibitors SSRIs are widely prescribed to treat depression. Although these drugs presumably have the same mechanism of action, they vary in several clinically important ways, including how long they remain in the body and the extent to which they interfere with the metabolism of other medications.
This article reviews What is the least sedating ssri pharmacologic differences among SSRIs and how these differences may affect various aspects of treatment, such as dosing, administration, and discontinuation. Understanding the distinct properties of SSRIs may help primary care physicians to design the most appropriate therapeutic plan for individual patients. Depression is as common as—and often more debilitating than—chronic medical ailments such as arthritis and diabetes. In addition to increasing the risk of suicide, it may hasten the onset or worsen the course of other serious illnesses.
Patients who have suffered a myocardial infarction, for example, tend to die sooner if they also suffer from depression.
Most patients with symptoms of affective disorders seek treatment in primary care settings 7 ; thus, primary care physicians play an important role in the diagnosis and management of depression. The introduction of selective serotonin reuptake inhibitors SSRIs more than a decade ago simplified the treatment of depression in primary care settings.
They also are relatively free of serious side effects, such as urinary retention and slowed conduction.
Consequently, patients who are prescribed SSRIs do not require extensive pharmacologic monitoring e. SSRIs including citalopram, fluoxetine, fluvoxamine which is approved What is the least sedating ssri obsessive-compulsive disorder but is often used for depressionparoxetine, and sertraline are similarly efficacious 8—13 but have distinct pharmacologic profiles. Understanding the differences among the SSRIs may help primary care physicians determine which agent to prescribe and what What is the least sedating ssri to take when designing a treatment plan for an individual patient.
SSRIs are chemically diverse and thus differ from each other in several clinically important ways, including 1 how effective they are across their recommended dose range, 2 how efficiently they are metabolized across their dose range kinetics3 how quickly they are eliminated from the body half-life4 how patient age affects their elimination, and 5 how they affect the metabolism of other drugs see Table 1.
In addition, they may differ slightly in the way they affect various targets in the body i. These individual differences can influence dosing and administration among general and "What is the least sedating ssri" populations e. Thus, most patients who are prescribed sertraline will probably require upward dose adjustments.
This is an important consideration, since administering insufficient doses of an antidepressant can result in treatment failure and unnecessary drug substitutions. Fluoxetine and paroxetine and possibly fluvoxamine inhibit their own metabolism, which can lead to disproportionate increases in plasma levels nonlinear kinetics at higher doses. However, as a precaution, physicians should prescribe reduced doses of fluoxetine, fluvoxamine, and paroxetine to patients whose ability to eliminate drugs is already substantially impaired e.
The human aging process is accompanied by reductions in liver and kidney function that can extend the half-life and increase the blood levels of many drugs, including some of the SSRIs. As shown in Table 1dose adjustments are recommended when prescribing citalopram, paroxetine, and fluvoxamine to elderly patients.
In clinical trials, SSRIs have been well tolerated compared with placebo. Their benign cardiovascular profile and broad therapeutic range make them relatively safe in overdose.
Common side effects associated with SSRI therapy include nausea and sexual dysfunction. Although the SSRIs are well tolerated as a class, their distinct secondary effects on the body i. For example, significant weight loss may benefit obese patients but may be hazardous to patients who are frail. Likewise, activating effects can be helpful for patients with extreme psychomotor retardation but can lead to added distress and polypharmacy e.
Although it is impossible to anticipate exactly how a given person will respond to a particular SSRI, consideration of possible differences in secondary effects may help the clinician to make the most favorable match between patient and drug. Depression often requires months or even years of continuous pharmacotherapy. Thus, it is quite likely that many patients will take at least 1 other drug—be it an over-the-counter cough syrup, a nasal decongestant, or an antibiotic—with their SSRI at some time during treatment.
For some patients e. SSRIs are relatively safe when administered alone, but the risk of combining them with other medications varies significantly from agent to agent. Underlying this variability is the cytochrome P CYP system, a group of enzymes that metabolizes most marketed drugs. All of the SSRIs are extensively biotransformed by the P system, but fluoxetine, fluvoxamine, and paroxetine also significantly inhibit 1 or more of the major P enzymes.
In contrast, citalopram and sertraline do not substantially inhibit P enzymes. When initiating therapy with an SSRI, the single most important means of avoiding adverse drug interactions is to make a list of every medication the patient is taking.
On the basis of this inventory and what is known about the P system, physicians can predict which antidepressants are least likely to conflict with an existing regimen. If a patient has already been prescribed an SSRI with a high potential for Pmediated drug interactions, several steps can be taken to avoid problematic situations when other forms of therapy are initiated.
The first step is to become familiar with the drugs that are most likely to interact with the particular SSRI in a clinically meaningful way. These include agents that become toxic with relatively minor elevations above the therapeutic dose Table 3 or are inactive in their unmetabolized form e. In either case, the best course is to select an alternative medication, if one is available.
For example, ibuprofen or another nonopiate analgesic could be substituted for codeine to treat minor pain. Likewise, an antiarrhythmic drug not in class IC could be prescribed instead of propafenone. If a safer What is the least sedating ssri does not exist, agents with a narrow therapeutic range that are quite likely to be affected by an SSRI should be started at a lower-than-usual dose, and the patient should be closely monitored for adverse reactions.
Self-medication with over-the-counter preparations, leftover or borrowed prescription drugs, and alternative medicines e. Therefore, educating the patient about the risks of combining SSRIs either individually or as a class
What is the least sedating ssri other drugs is a critical component of safe and effective therapy. For example, patients taking fluvoxamine for either depression or obsessive-compulsive disorder should be cautioned against the use of benzodiazepines outside of a doctor's care, since interactions between fluvoxamine and benzodiazepines can cause oversedation.
Two commonly self-administered drugs that have the potential to interact with all SSRIs are dextromethorphan, an ingredient in many cough syrups, and St. John's wort Hypericum perforatuman increasingly popular herbal antidepressant. Both agents affect serotonin in fact, a constituent of St. John's wort appears to be a naturally occurring serotonin uptake inhibitor and therefore may have additive effects when combined with SSRIs.
Coprescribing SSRIs with monoamine oxidase inhibitors is contraindicated because of the possibility of such reactions. To avoid potentially serious clinical situations, physicians should inform patients about both the risks and the warning signs of adverse interactions between SSRIs and other commonly used and abused serotonergic drugs, including meperidine and amphetamines.
Lithium and buspirone are commonly coprescribed with antidepressants to boost efficacy. Although lithium is not susceptible to Pmediated drug interactions, it appears to have nonspecific serotonergic effects and therefore may interact with SSRIs in the manner described above.
Buspirone is metabolized by the CYP3A4 enzyme, which is substantially inhibited by fluvoxamine. The elderly, as a group, tend to take many medications on a daily basis. Because the aging body eliminates drugs less efficiently and is more sensitive to pharmacotherapeutic side effects, adverse reactions resulting from drug-drug interactions are not only more common but also potentially more severe and longer lasting in older patients.
Choosing an agent with a low propensity for drug interactions is therefore especially important for the management "What is the least sedating ssri" late-life depression. All drug combinations should be carefully monitored among elderly patients who are frail or medically ill. Withdrawal effects can occur when any antidepressant is abruptly discontinued.