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Atypical Antipsychotics

The Atypical Antipsychotics are also known as Novel or Second-Generation Antipsychotics because they were introduced decades after the Typical Antipsychotics had been developed. Whereas the Typical Antipsychotics target psychotic symptoms by blocking the actions of dopamine in the brain, the Atypicals tend to be less potent dopamine blockers while targeting a variety of other neurotransmitter systems, including serotonin, which seems to have an important role in their functioning. This means that the Atypicals are effective in treating psychosis while causing lower rates of extrapyramidal side-effects than the Typical Antipsychotics.

It was for this reason that the Atypical Antipsychotics became quite popular when they were introduced, and why they have now very much supplanted the Typical Antipsychotics in popularity of use, especially in North America. However, more recent data suggests that some of this initial enthusiasm may have been somewhat unfounded. Atypical Antipsychotics do not necessarily cause lower rates of extrapyramidal side-effects than low-potency Typical Antipsychotics [ref]. They are also known to lead to significant weight gain and other metabolic problems, like elevated blood sugar and cholesterol, in many people who take them.

Uses of Atypical Antipsychotics

In addition to treating psychosis, the Atypicals can be used for treating a number of other symptoms and conditions in people who do not have any psychotic symptoms. This includes:

Weight gain and Metabolic Side-Effects of Atypical Antipsychotics

Weight gain and metabolic side-effects (insulin resistance, elevated glucose and lipids) have actually been a very significant problem for many individuals taking these medications. These side-effects are concerning not only because weight gain can cause people to feel unattractive and to experience low self-esteem, but also because these are powerful risk factors for developing serious medical complications such as diabetes, heart disease and strokes.

Among the atypical antipsychotics, Olanzapine and Clozapine seem to cause, on average, the greatest amount of weight gain and metabolic side-effects, and in the largest percentage of individuals (about 30% of individuals taking Olanzapine, and 50% of individuals taking Clozapine, will gain more than 7% of their body weight from these medications) [ref, ref].

Lurasidone, Aripiprazole, Ziprasidone and Amisulpride tend to cause the lowest rates of these side-effects, though, contrary to popular belief, the rates of weight gain and metabolic side-effects caused by these three medications are not zero [ref, ref]. Lurasidone may be the atypical antipsychotic with the lowest risk of these side-effects compared to all others, though further studies are needed to clarify this point [ref].

Quetiapine, Risperidone and Asenapine lay somewhere in the middle ground when it comes to these side-effects, causing a weight of 7% of more of one's body weight in about 15-20% of individuals [ref, ref].

Preventing and treating weight gain and metabolic side-effects of Atypical Antipsychotics

Several studies have found that these side-effects of weight gain and metabolic changes can in many cases be prevented or reversed by adding Metformin [ref, ref, ref, ref, ref]. Topiramate has also been found in some studies to prevent or treat atypical antipsychotic-induced weight gain [ref, ref].

Orlistat is a medication that prevents fats from being absorbed from the intestinal tract; there is some preliminary evidence that this medication may help treat weight gain caused by atypical antipsychotics [ref].

Reboxetine, Sibutramine and Amantadine may all help some patients lose weight [ref]. However, these medications may pose problems for some individuals with certain psychiatric conditions. Reboxetine and Sibutramine both have antidepressant properties that may lead to mood instability in people of Bipolar Disorder, while Amantadine stimulates dopamine and may worsen manic or psychotic symptoms in some patients.

Histamine-2 (H2) blockers, namely Nizatidine, Ranitidine, and Famotidine, are a class of medications that have shown positive results in some studies, but negative results in others [ref] for treating atypical antipsychotic-induced weight gain or metabolic symptoms. Based on these inconsistent findings, their use is not supported for this purpose.

List of Atypical Antipsychotics

Amisulpride (Solian): Not available in the US or Canada, but used commonly in other countries. In addition to the other common uses of Atypical Antipsychotics, this medication can also be used on its own to treat Depressive Disorders.

Aripiprazole (Abilify): This medication tends not to cause significant weight gain or metabolic side-effects. It has also been marketed as helping to resolve Negative Symptoms of Schizophrenia. It may cause higher rates of extrapyramidal side-effects than the other Atypicals.

Asenapine (Saphris, Sycrest): Recently released onto the market.

Iloperidone (Fanapt): Recently released onto the market.

Lurasidone (Latuda): Recenty released onto the market, seems to have a very low risk of causing weight gain and metabolic side-effects and may also be particularly effective for treating Bipolar Depression [ref, ref] in addition to its other indications.

Olanzapine (Zyprexa): Some studies have found this medication to be among the more effective antipsychotics for treating Schizophrenia [ref], but it has one of the highest rates of causing weight gain and metabolic side-effects.

Paliperidone (Invega): This medication is a derivative of Risperidone.

Perospirone (Lullan): Available mainly in China and Japan.

Quetiapine (Seroquel, Seroquel XR): In addition to the other common uses of Atypical Antipsychotics, this medication stands out as being effective on its own for treating Bipolar Depression, Unipolar Depression, and Generalized Anxiety Disorder. During the first week or two of use it can cause significant sedation and dizziness, but with time and at higher doses these side-effects usually dissipate.

Risperidone (Risperdal, Risperdal CONSTA): This medication is the most potent dopamine blocker among the Atypical Antipsychotics, which means that it tends to cause more extrapyramidal side-effects than the other Atypicals and to act more like a Typical Antipsychotic at doses above 6mg/day.

Sertindole (Serdolect): Was withdrawn from the market in 1998 because of concerns of it causing serious heart arrhythmias. Subsequent studies have found that this medication seems to be safe, and it is once again being used in various countries.

Sulpride (Meresa, Sulpirid, Bosnyl, Dogmatil, Eglonyl, Sulpiryd): Not available in the US or Canada.

Ziprasidone (Geodon, Zeldox): This medication tends not to cause significant weight gain or metabolic side-effects.

Zotepine (Nipolept, Losizopilon, Lodopin, Setous): Available mainly in Germany and Japan.


Note: Some authorities include Clozapine among the Atypical Antipsychotics, but PsychVisit sees Clozapine as being in its own special category (see here for further information).