5 anxiety disorders

PHARMACOLOGY 27soon see that for all of our knowledge about what psychiatric medications do, weoften fall short of knowing exactly how they work.When we talk about what a psychiatric medication does, we are invariably discussingits effect on neurotransmission between nerve cells across the synapse.Psychiatric medications act by modulating chemical neurotransmission in thesynapse. However, as you probably know, it often takes several days or weeks fordepression or psychosis to respond to treatment. Clearly, psychiatric medicationswork. Why, however, is there often a delay before they begin to do so?Initiation and Adaptation. The answer to this question is surprisingly simple.Many psychiatric medicines do not work immediately because they work indirectly.By changing neurotransmission, these medicines set in motion a sequenceof events in the brain. As brain neurochemistry gradually changes in response tothe sustained alterations in neurotransmission produced by the psychiatric medicine,the therapeutic effects of the medication become evident. Taking the medicationinitiates the process, but the adaptation made by the brain to the continuedpresence of the medication is what ultimately determines whether or not there is aresponse.These paired processes, known as initiation and adaptation, do not represent anew concept. We’ve long known that taking a drug one time can have very differenteffects from taking it repeatedly. Perhaps the most familiar examples are the drugsof abuse. For example, the acute effect of cocaine is to produce an intense but briefeuphoria. Cocaine produces this effect by enhancing neurotransmission in dopamine-activatedreward circuits in the brain. These “initiating” effects happen veryquickly in response to the action of cocaine in the synapse.Some psychiatric medications also produce a response within minutes of takinga single dose. Their therapeutic benefit can come very quickly. For example, takinga benzodiazepine such as diazepam (Valium) can quickly relieve panic and anxiety.Taking a stimulant can often rapidly relieve the symptoms of attention deficit–hyperactivitydisorder (ADHD). When psychiatric medications work this quickly, weassume that the therapeutic benefit is a direct consequence of their “initiating” actionin the synapse.Side effects can also occur quickly after a single dose of a medication. Forexample, some antidepressants (e.g., selective serotonin reuptake inhibitors) cancause nausea, stomach upset, loose stools, and even diarrhea. Likewise, some antipsychotics(e.g., haloperidol (Haldol)) can cause unpleasant or painful muscle spasmscalled dystonias. All of these side effects can occur within minutes or hours oftaking a single dose of the medication. These side effects are also a result of thedirect effects of the medication in the synapse.However, the long-term effects of habitually taking a medication or a substanceof abuse can be quite different. For example, when cocaine is used repeatedly, itproduces long-lasting changes in the brain’s reward regions that precipitate thebehavioral manifestations of addiction such as drug craving and, ironically, the lossof the originally experienced euphoria. This represents the adaptation, or we mightargue the maladaptation, of the brain to habitual cocaine use.