Magazine article Clinical Psychiatry News

Soothing the Anxious Patient: Calculated Combinations

Magazine article Clinical Psychiatry News

Soothing the Anxious Patient: Calculated Combinations

Article excerpt

Issue Medication combination is often necessary to achieve optimal anxiety control.

Actions Combining medications with different mechanisms of action can be synergistic.

Benefits Understanding the mechanisms of action of medication classes can result in improved patient response, lessened anxiety, and avoid unnecessary duplication of neurochemical effect.

When we treat generalized anxiety disorder, social anxiety disorder, panic disorder, or symptomatic anxiety in bipolar disorder or depression, a common prescribing challenge is to minimize excess anxiety. This month, we begin with our anxiolytic treatment staples and explore newer medication classes that have been added to our tool kit.

The bread and butter basics

For several years, intelligent practitioners have moved from benzodiazepine monotherapy to antidepressant monotherapy--selective norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs)--as first-line treatment for anxiety. When using antidepressants for anxiety treatment, several clinical strategies are useful:

* Because anxiety patients can be very sensitive to the effects of antidepressants, start with very small doses of the antidepressant; Use liquid preparations to administer microdoses if necessary

* Initially, add a benzodiazepine with its added GABAergic effect to the antidepressant, then taper the benzodiazepine after 4-6 weeks; Some patients will need both medications long-term for full symptom control; Chronic use of both agents can be safe and effective maintenance treatment when indicated

What else can we do?

Knowing the different mechanisms of action of additional, newer agents helps the informed clinician decide on medication combinations while avoiding unnecessary and unhelpful duplication. By using medications with complementary and additive mechanisms of action, increased symptom control is possible, thereby converting partial responders into full responders.

GABA and glutamate have opposing effects

Gamma-aminobutyric acid (GABA) is present in almost all areas of the brain and is a primary inhibitory compound for stress-induced brain response. GABA calms and "quiets" the brain, and neurophysiologically minimizes the neurochemical effects produced by stress. Therefore, when we increase GABA transmission, we decrease the brain's stress response and decrease the patient's anxiety.

Glutamate has an opposite neural effect. While GABA is inhibitory, soothing, and calming, glutamate is excitatory and leads to increased anxiety. Therefore, medications that decrease glutamate in brain synapses lead to decreased anxiety and are potential anti-anxiety agents. Thus, the following two medication groups exert their anti-anxiety effect by very different methods.

Tiagabine--a GABA reuptake blocker

Benzodiazepines, which work directly on the GAB[A.sub.A] receptor site to increase GABA transmission, have long been our primary GABAergic agents. Tiagabine (Gabitril) increases GABA transmission by a totally different mechanism. It blocks the reuptake of the GABA transporter in the synapse, thus functionally increasing GABA transmission. This is analogous to SSRIs' increase of serotonin by blocking the reuptake of the serotonin transporter. Eight to thirty-two mg of tiagabine can provide useful anti-anxiety effects and, in some patients, serves as a nonaddictive hypnotic. When used for anxiety, two to three smaller doses per day are prescribed. …

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