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 Depression  Holistic-online.com

Serotonin Antagonists

Serotonin Antagonists boost serotonin by blocking its reuptake at nerve synapses, much like the SSRIs. Examples of Serotonin Antagonists are: trazodone (Desyrel) and nefazodone (Serzone). They are useful in case of persons suffering from anxiety and depression.

Trazodone and nefazodone appear to block some of the scrotonin receptor sites on post-synaptic nerve membranes called the 5-HT2A and 5-HT2C receptors. (5-HT stands for serotonin. The number and letter after the 5-HT identify the specific type of receptor.) While blocking the serotonin 2A and 2C receptors, trazodone and nefazodone indirectly stimulate another type of serotonin receptor called the 5-HT1A receptor. Serotin 1A receptor is thought to be important in depression, anxiety, and violence. According to one theory, the stimulation of these serotonin 1A (5HT1A) receptor sites might explain the antidepressant effects of trazodone and nefazodone. Trazodone and nefazodone are also effective anti-anxiety drugs. Thus, they are often prescribed for persons who are nervous and worried in addition to being depressed.

Doses of Trazodone and Nefazodone

The starting dose for trazodone is 50 to 100 mg per day. Most common dose is 150 mg to 300 mg per day.

The starting dose for nefazodone is 100 mg twice per day.

The doses of both drugs can be increased very slowly over several weeks to a maximum of 600 mg per day.

Side Effects of Trazodone and Nefazodone

Side Effects of Nefazodone

Dry mouth and throat
Blurred vision
Abnormal vision

Side Effects of Trazodone

Dry mouth and throat
Upset stomach
Blurred vision
Priapism (rare, see discussion)

Stomach upset (such as nausea) is a common side effect of serotonin antagonists especially when the medicine is taken on an empty stomach. Take it with food to minimize this.

Trazodone and nefazodone may cause dry mouth in some patients.


Both drugs can cause a temporary drop in blood pressure when you stand up, resulting in dizziness or light-headedness. This is more likely in case of Trazodone than nefazodone. To minimize this problem:

bulletGet up more slowly
bulletWalk in place when you get up so as to "pump" blood back to your heart from your legs
bulletUse support stockings
bulletTake adequate amounts of fluid and salt to prevent any dehydration


This is sometimes observed as a side effect of trazodone. Priapism involves an involuntary erection of the penis. It is quite rare. (about one male patient out of 6,000.) If you experience this side effect, it need to be treated immediately. (Call your doctor or go to the emergency room immediately if you notice this.) Otherwise, it can lead to damage of the penis and permanent impotence (the inability to get an erection). Some patients may require surgery to correct the priapism. Injecting a drug like epinephrine directly into the penis can sometimes counteract the priapism if you catch it quickly enough. Nefazodone does not cause priapism.

Drug Interactions for Trazodone and Nefazodone

Nefazodone has the effect of raising the blood level of a number of drugs.

Anxiety Drugs

Nefazodone has the effect of raising the blood level of a number of commonly prescribed drugs for anxiety, including many of the minor tranquilizers such as alprazolam (Xanax), triazolam (Halcion), buspirone (BuSpar) and others. Be very careful when combining these drugs with nefazodone. You could become excessively sleepy.


Trazodone or nefazodone can enhance the sedative effects of any drug that makes you sleepy, such as alcohol, barbiturates, sleeping pills, painkillers, some major tranquilizers (neuroleptics), and some antidepressants. Be very cautious if you combine any sedative agents with nefazodone or trazodone, especially if you are driving or operating dangerous machinery.

Tricyclic Antidepressants

Nefazodone can increase the levels of several tricyclic antidepressants in your blood, especially amitriptyline (Elavil), clomipramine (Anafianil), and imipramine (Tofranif). Your doctor will have to adjust the doses of these drugs downward if taken together.

SSRI Antidepressants

If nefazodone and one of the SSRIs are combined, there is the possibility that a metabolite of nefazodone called MCPP (m-chlorophenylpiperazine) could build up in your blood. This substance may lead to agitation or feelings of panic or unhappiness

MAOI Antidepressants

Neither trazodone nor nefazodone should be combined with an MAOI antidepressant because this combination could trigger the dangerous serotonin syndrome (hyperpyrexic crisis).

Blood Pressure Medications

Your blood pressure may drop more than expected if you combine trazodone with a blood-pressure medication. If your blood pressure does drop too much, you may notice dizziness when you suddenly stand up.

Anticonvulsants and Heart Medications

Trazodone can cause increased blood levels of the anticonvulsant phenytoin (Dilantin) and the heart medication digoxin (Lanoxin). These combinations can lead to toxic blood levels of phenytoin or digoxin. Your blood levels of phenytoin or digoxin have to be monitored carefully if you take trazodone.

Blood Thinner

The levels of warfarin may increase or decrease if you combine it with trazodone. The results, in other words, is unpredictable. If the warfarin level increases, you may have a greater tendency to bleed, and if it decreases, your blood may have a greater tendency to clot.


The combination of nefazodone and two commonly prescribed antihistamines that are given for allergies terfenadine (trade name Seldane), and astemizole (trade name Hismanal) can be very dangerous and should be avoided. Nefazodone causes the levels of these two anti- histamines to increase. This, in turn, can result in changes in heart rhythms that may have fatal consequences.

Do not combine nefazodone with cisapride (trade name Propulsid, a stimulant for the gastrointestinal tract). This can also result in sudden fatal heart failure.

See Also: 

Tricyclic Antidepressants

The Monoamine Oxidase Inhibitors (MAOI)

Selective Serotonin Reuptake Inhibitors (SSRIs)

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