Think beyond benzodiazepines for anxiety

An excerpt from Understanding Medicines for Anxiety.

Although the SSRIs (selective serotonin reuptake inhibitors) are among the most widely prescribed medicines for depression, they also have a useful role to play in treating anxiety disorders. In this article, we will look at their benefits and limitations when used in this manner.

Since their introduction into the market in the 1980s, the SSRIs have been found to have a number of advantages over the older antidepressants, among which are a better side effect profile and relatively lower toxicity in overdose.
As more experience was gained, it became clear that they are also beneficial for anxiety, and several received FDA approval for generalized anxiety disorder and ultimately other conditions, including panic disorder, obsessive-compulsive disorder (OCD) and PTSD. In 1993, a related class of antidepressants, the SNRIs (serotonin-norepinephrine reuptake inhibitors) became available, and later two of them, duloxetine and venlafaxine, were also approved for anxiety disorders.

The SSRIs and SNRIs differ somewhat from the benzodiazepines in the way they affect depression. While benzodiazepines may reduce anxiety symptoms within hours, the benefits of these drugs are most evident after two to six weeks. Thus, they are often used more as a longer-term treatment. They are often continued for 6-12 months after symptoms improve, to reduce the risk of relapse. They have some advantages over benzodiazepines, in that they are less sedating and have a generally better side-effect profile with less concern about memory and coordination difficulties. One major advantage is in persons with both anxiety and depressive symptoms. In this situation, benzodiazepines will not help the depression and may potentially make it worse. In contrast, antidepressants can be of benefit to both types of symptoms. Unlike benzodiazepines, SSRIs and SNRIs are not generally considered drugs of abuse and are not DEA scheduled drugs.

Side effects: Drowsiness is among the most common side effects of these drugs. Disturbances of sexual dysfunction, including diminished libido, anorgasmia, and erectile difficulties may occur and are more likely with paroxetine and sertraline. Sometimes there is a brief period of increased anxiety when starting these medicines. Serotonin also plays a role in gastrointestinal function, leading to SSRI side effects of nausea or diarrhea, particularly with sertraline. There can be bleeding from the upper gastrointestinal tract. Weight gain can occur, perhaps more commonly with paroxetine and less likely with fluoxetine. Insomnia may become a problem, as well as anticholinergic symptoms. Duloxetine should be avoided in persons with narrow-angle glaucoma; it may also rarely cause harm to the liver. Like all antidepressants, SSRIs and SNRIs carry an FDA warning about the possibility of increased suicidal ideation or behavior in children, adolescents and young adults. Antidepressants can also lengthen the QTc interval. Allergic reactions producing rash or itching are possible.

Although relatively less common, some persons may develop asthenia, with apathy and a sense of having less mental energy and a kind of emotional blandness. Particularly in someone with depression, it can be difficult to distinguish from the decreased energy that is part of the original condition. If other symptoms are getting better at the same time that apathy and blandness are appearing, it may be more likely that this represents drug-induced asthenia.

One potential adverse effect of SSRIs of particular concern is serotonin syndrome, with symptoms including confusion, muscle rigidity, agitation, diarrhea, hypertension, and tachycardia. Sometimes this can happen from a single drug, particularly if taken in overdose, but it can also result from taking two different drugs which each have serotonergic effects.

Stopping SSRIs and SNRIs can cause a variety of disturbances in roughly 20%, with dizziness, headaches, agitation, depressed mood, numbness, and tingling sensations. This may be more common with paroxetine, and with all these drugs is most prominent after abrupt discontinuation. Traditionally, tapering before discontinuation has been done over the course of a month or so. There has been increasing recognition in recent years that some patients may be susceptible to very prolonged withdrawal symptoms. Recommendations are currently evolving, but there is a growing belief that for many patients tapering is best accomplished very gradually, often over a period of several months or longer.

Choosing which one: There is little evidence that any particular SSRI or SNRI is more effective than others for generalized anxiety disorder, though some believe that fluoxetine is the most effective. It is not uncommon for one to seem to have minimal benefit, leading to trying a different one. Fluoxetine, which takes longer to reach peak blood levels and because of its long half-life, takes longer to reach steady state, and might be slower in the onset of effect. Others may differ by side-effect profile.

Paroxetine, for instance, may be more likely to cause sedation or sexual dysfunction. Sertraline is probably the SSRI with the lowest likelihood of troubling side effects. The SSRIs with the least likelihood of interfering with the metabolism of other drugs are sertraline, citalopram, and escitalopram.

Duloxetine, in addition to having antidepressant and anti-anxiety effects, is helpful in some pain conditions such as fibromyalgia and diabetic neuropathy and may be a good choice in persons with anxiety who also have one of these. For panic disorder, the best choices would be the antidepressants which have been specifically tested and approved for this purpose: fluoxetine, paroxetine, sertraline, and venlafaxine.

In summary, the SSRIs and SNRIs offer many advantages over older drugs for anxiety. Their main limitation is that it generally takes several weeks for benefits to be fully manifest. It is worthwhile to have a healthy respect for some adverse effects that are sometimes not considered, including asthenia, the risk of serotonin syndrome and prolonged withdrawal difficulties.

Wallace B. Mendelson is a psychiatrist and author of Understanding Antidepressants and Understanding Medicines for Anxiety.

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