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Section 30
Atypical Antidepressant Medications

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Selective serotonin reuptake inhibitors (SSRIs) are medications that increase the amount of the neurochemical serotonin in the brain. Brain serotonin levels are low in depression. The SSRIs work by selectively inhibiting or blocking serotonin reuptake in the brain. This block occurs at the synapse, the place where brain cells are connected to each other. Serotonin is one of the chemicals in the brain that carries messages across these connections from one neuron to another. The SSRIs work by keeping the serotonin present in high concentrations in the synapses. These drugs do this by preventing the reuptake of serotonin back into the sending nerve cell. The reuptake of serotonin is responsible for turning off the production of new serotonin. Therefore, the serotonin message keeps on coming through. This, in turn, helps arouse or activate cells that have been deactivated by depression, and relieves the depressed person’s symptoms. In the United States, SSRIs have been used successfully for over a decade to treat depression.

Examples of SSRIs include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), and fluvoxamine (Luvox). SSRIs are generally well tolerated and side effects are usually mild. The most common side effects are nausea, diarrhea, agitation, insomnia, and headache. However, these side effects generally go away within the first month of SSRI use. Some patients experience sexual side effects, such as decreased sexual desire, delayed orgasm, or an inability to have an orgasm. Some patients experience tremors with SSRIs. The so-called serotonergic (meaning caused by serotonin) syndrome is a serious neurologic condition associated with the use of SSRIs. It is characterized by high fevers, seizures, and heart rhythm disturbances. This condition is very rare and has been reported only in very ill psychiatric patients taking multiple psychiatric medications.

Dual Action Antidepressants: The biochemical reality is that all classes of medications that treat depression (MAOIs, SSRIs, TCAs, and atypical antidepressants) have some effect on both norepinephrine and serotonin, as well as on other neurotransmitters. However, the various medications affect the different neurotransmitters in varying degrees.

Some of the newer antidepressant drugs, however, appear to have particularly robust effects on both the norepinephrine and serotonin systems. These drugs seem to be very promising, especially for the more severe and chronic cases of depression. (Psychiatrists, rather than family practitioners, see such cases most frequently.) Venlafaxine (Effexor) is one of these dual action compounds. It is a serotonin reuptake inhibitor that, at lower doses, shares many of the safety and low side effect characteristics of the SSRIs. At higher doses, this drug appears to block the reuptake of norepinephrine. Thus, venlafaxine can be considered an SNRI, a serotonin and norepinephrine reuptake inhibitor.

Another newer antidepressant, mirtazapine (Remeron), is a tetracyclic compound (four-ring chemical structure). It works at somewhat different biochemical sites and in different ways than the other drugs. It affects serotonin, but at a post-synaptic site (after the connection between nerve cells.) It also increases histamine levels, which can cause drowsiness. For this reason, mirtazapine is given at bedtime and is often prescribed for people who have trouble falling asleep. Like venlafaxine, it also works by increasing levels in the norepinephrine system. Other than causing sedation, this medication has side effects that are similar to those of the SSRIs, but to a lesser degree in many cases.

Atypical antidepressants are so named because they work in a variety of ways. Thus, atypical antidepressants are not SSRIs, but they act similarly. More specifically, they increase the level of certain neurochemicals in the brain synapses. Examples of atypical antidepressants include nefazodone(Serzone), trazodone (Desyrel), venlafaxine (Effexor), and bupropion (Wellbutrin). Lithium (Eskalith, Lithobid), valproate (Depakene, Depakote), carbamazepine (Epitol, Tegretol), neurontin (Gabapentin), and lamictal (Lamotrigine) are mood stabilizers and anticonvulsants. They have been used to treat bipolar depression. Certain antipsychotic medications, such as ziprasidone (Geodon), risperidone (Risperdal), and quetiapine (Seroquel), have sometimes also been used to treat bipolar depression, usually in combination with other antidepressants and/or the mood stabilizers.

“Personal Reflection” Journaling Activity #10
The preceding section was about Medications for Depression. Write three case study examples regarding how you might use the content of this section of the Manual in your practice.

QUESTION 30:
What medication is a serotonin reuptake inhibitor that, at lower doses, shares many of the safety and low side effect characteristics of the SSRIs; and at higher doses, this drug appears to block the reuptake of norepinephrine? To select and enter your answer go to Answer Booklet.