The Best Antidepressants for Irritability

Antidepressant medications are prescribed for irritability when a chemical imbalance is suspected as being the etiology of the unwanted mood disturbance. Many medications approved by the U.S. Food and Drug Administration that are intended for the treatment of depressive disorder have positive effects on anxiety levels as well. Irritability is often seen as a secondary symptom of a condition presenting on the anxiety spectrum. For this reason, certain antidepressants tend to be on the front line of treatment across many psychiatric practices.

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Paroxetine, a chemical that works almost exclusively on serotonin in the brain, is the only medication on the U.S. market that is approved to treat all accepted disorders on the anxiety spectrum. This is one reason it is used often as a first defense if you seek help for your anxiety condition. A study appearing in the October 2001 issue of “Psychopharmacology” deals with the specific role serotonin plays in social dominance and affiliative behavior, both variables that may contribute to pronounced irritability in social situations. The study concluded that significant symptomatic relief was seen in patients who had been on paroxetine for four to six weeks; they showed less hostility and more socialization. Another study in the 2007 issue of the “Cochrane Database of Systematic Reviews” focused exclusively on generalized anxiety disorder, a factor bringing it to the forefront of this debate because the condition is many times diagnosed in the presense of irritability and restlessness. The study compared the efficacy of selective serotonin reuptake inhibitors like paroxetine versus a placebo pill for treatment. Paroxetine and an unrelated antidepressant drug, imipramine, performed significantly well. The major complaint by patients who take paroxetine is its sometimes prolonged and uncomfortable withdrawal


Venlafaxine is a serotonin and norepinephrine reuptake inhibitor. Dr. Wayne C. Jones of Texas reports that it is often the first course of treatment in his practice because of its quick onset; in some cases, major changes are seen after only seven days. Due to its status as a norepinephrine inhibitor, the drug sometimes causes nausea or jitters while the body reaches peak plasma levels and becomes used to the change of chemical percentages. Despite these side effects, venlafaxine is generally well tolerated and does not have many adverse drug interactions. Its efficacy was tested in a study published in the “Journal of the American Medical Association” in 2007. The two doctors in charge of the study, James L. Levenson and Robert K. Schneider, concluded that venlafaxine was significantly more effective than the placebo for the treatment of generalized anxiety disorder.


Imipramine belongs to an earlier class of antidepressant medications, tricyclics. While the medication is not usually used as a first-line defense in the treatment of anxiety or depression, it is still used frequently when other medicines fail to be effective. Dr. Laszlo A. Papp of Brown University explains that during the early 1960s, it was the first non-addictive medication to show efficacy in treating disorders on the anxiety spectrum. Its efficacy is still competitive in today’s saturated antidepressant market because, as was mentioned earlier, imipramine was reported to be on par with paroxetine in the study from 2007.


Sertraline, another selective serotonin reuptake inhibitor, was approved for the treatment of anxiety, with or without concurrent depression, early after the tricyclics became less popular with prescribing physicians. It is sometimes thought of as the “gold standard” by which to compare other antidepressant medications. For example, the University of Michigan used sertraline in a study done in 2008 as its base medication while testing other possible candidate medications for depression and anxiety. Sertraline is generally considered the safest for adolescents and pregnant mothers, as well, keeping it near the top of the list of medications used to treat anxiety and depression.