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