| Antidepressants are used commonly in medical and | | | | respond to the serotonin-selective tricyclic |
| psychiatric practice. As a class, antidepressants have | | | | clomipramine (Anafranil) and to SSRIs at high doses |
| in common their ability to treat major depressive | | | | (e.g., fluoxetine at 60-80mg/ day). Obsessions tend |
| illness. Most antidepressants are also effective in the | | | | to be more responsive to pharmacotherapy than |
| treatment of panic disorder and other anxiety | | | | compulsions. Symptoms of OCD respond more slowly |
| disorders. Some antidepressants effectively treat | | | | than symptoms of major depression. Trials of 12 |
| obsessive-compulsive disorder (OCD) and a variety of | | | | weeks or more are needed before a medication can |
| other conditions (see indications below).The most | | | | be ruled a failure for an OCD patient.The binging and |
| commonly prescribed antidepressants are listed in | | | | purging behavior of bulimia has been shown to |
| Table 12-1. Antidepressants are subdivided into | | | | respond to SSRls, TCAs, and MAOls in several open |
| groups based on structure or prominent functional | | | | and controlled trials. Because SSRIs have the most |
| activity: selective serotonin reuptake inhibitors | | | | benign side-effect profile of these medications, they |
| (SSRls), tricyclic antidepressants (TCAs), monoamine | | | | are often the first-line psychopharmacologic |
| oxidase inhibitors (MAOls), and other antidepressant | | | | treatment.Mechanisms of ActionAntidepressants are |
| compounds with a variety of mechanisms of action. | | | | thought to exert their effects at particular subsets |
| Antidepressants are typically thought to act on either | | | | of neuronal synapses throughout the brain. Their |
| the serotonin or norepinephrine systems, or both. | | | | major interaction is with the monoamine |
| Choice of medications typically depends on diagnosis, | | | | neurotransmitter systems (dopamine, norepinephrine, |
| history of response (in patient or relative), and the | | | | and serotonin). Dopamine, norepinephrine, and |
| side-effect profile of the medication. Antidepressant | | | | serotonin are released throughout the brain by |
| effects are typically not seen until 2 to 4 weeks into | | | | neurons that originate in the ventral brainstem, locus |
| treatment. Side effects must be carefully monitored, | | | | ceruleus and the raphe nuclei, respectively. These |
| especially for TCAs and MAOls.IndicationsTable 12-2 | | | | neurotransmitters interact with numerous receptor |
| lists the indications for antidepressants. | | | | subtypes in the brain that are associated with the |
| The main indication for antidepressant medications is | | | | regulation of global state functions including appetite, |
| major depressive disorder as defined by the | | | | mood states, arousal, vigilance, attention, and |
| Diagnostic and Statistical Manual of Mental Disorders, | | | | sensory processing.SSRls act by binding to |
| 4th edition (DSM-IV). Antidepressants are used in the | | | | presynaptic serotonin reuptake proteins, thereby |
| treatment of all subtypes of depression, including | | | | inhibiting reuptake and increasing the levels of |
| depressed phase of bipolar disorder, psychotic | | | | serotonin in the synaptic cleft.TCAs act by blocking |
| depression (in combination with an antipsychotic | | | | presynaptic reuptake of both serotonin and |
| medication), atypical depression, and seasonal | | | | norepinephrine. MAOls act by inhibiting the presynaptic |
| depression. Antidepressants also are indicated for the | | | | enzyme (monoamine oxidase) that catabolizes |
| prevention of recurrent depressive | | | | norepinephrine, dopamine, and serotonin, thereby |
| episodes.Antidepressant medications may be | | | | increasing the levels of these neurotransmitters |
| effective in the treatment of patients with | | | | presynaptically.These immediate mechanisms of |
| dysthymic disorder, especially when there are clear | | | | action are not sufficient to explain the delayed |
| neurovegetative signs or a history of response to | | | | antidepressant effects (typically 2 to 4 weeks). |
| antidepressants.Panic disorder with or without | | | | Other unknown mechanisms must play a role in the |
| agoraphobia has been shown to respond to SSRls, | | | | successful psychopharmacologic treatment of |
| MAOls, TCAs, and high-potency benzodiazepines | | | | depression. |
| (alprazolam and clonazepam).OCD has been shown to | | | | |