Data from Finland and other countries suggests that people with psychosis who regularly take antipsychotics live longer than patients who don’t. However, the long-term use of antipsychotics is also raising more and more questions and concerns recently. This blog is meant to inform about the current knowledge, to help people make the right decision.

Antipsychotics and health

Antipsychotics increase the risks of obesity, irregular heartbeat and problems with fat metabolism (the breaking down of fats by the body). Sometimes even so severely that they lead to insulin resistance and diabetes. With the newer, so-called second-generation antipsychotics this effect is stronger than with the first generation antipsychotics. These effects explain why antipsychotics are one of the factors that cause the shorter life expectancy among people under treatment for psychosis.

To cut a long story short: using antipsychotics over longer periods of time must be kept to a minimum, or when possible, avoided altogether. Their use requires an active plan to tackle the risks of weight gain and diabetes. Long-term studies show that at least 20 to 30 percent of people who are using antipsychotics are able to quit. Each person must find the right individual balance between the medicine’s protective effects and its toxic effects.

Antipsychotics and the brain

Neuro-imaging research (MRI scans) of the brains of people under psychosis reveal changes in brain activity. Some of these changes may be linked to the psychosis vulnerability itself (or to environmental risk factors that increase psychosis vulnerability, such as trauma), but many of these changes are clearly also related to several non-specific, external, factors, such as antipsychotics, smoking, obesity and drug use.

Animal tests have confirmed that antipsychotics indeed contribute to changes in the brain. The question remains, however, whether the changes in the brain caused by antipsychotics can also be linked to the specific risks. Also unknown is in how far these effects are permanent.

Antipsychotics and negative symptoms

Antipsychotics work by making people somewhat indifferent. This lowers the ‘importance’ or ‘significance’ of their psychosis, sometimes to the point where the symptoms fade away completely. The problem is, however, that this medicine-induced indifference does not only affect the psychosis, but every personal emotion or experience. The suppressing of emotions makes the user of antipsychotics more numb and less active. The extent to which this happens is different from person to person, but some are seriously impaired by it.

This indifference is also called ‘secondary negative symptoms’. That term is confusing however, because it is impossible to make a distinction between the primary symptoms (caused by psychosis) and the secondary symptoms (caused by the antipsychotics).

In practice, the rule should be: negative symptoms (indifference, inaction) must be attributed to the antipsychotics unless proven otherwise.

In other words: these symptoms require treatment, and should not be regarded as a consequence of psychosis when the real cause is the medication.

Can antipsychotics make psychosis worse? Dopamine supersensitivity syndrome (DPS)

When taking antipsychotics over a long time, the body will try to compensate the effects of the medication. Because antipsychotics work by blocking the dopamine receptor D2 in the brain, the body responds by trying to remove this blockade some way or another. As early as in the 1960’s, the scientist Chouinard described how this can cause “supersensitivity” in the dopamine D2 receptor. As such, the eventual effect can be an increase of psychosis sensitivity instead of the expected decrease.

Symptoms of dopamine supersensitivity syndrome:

• Abnormal movements – also called tardive dyskinesia
• Increased psychosis vulnerability
• Increase of the dosage required to suppress psychosis
• More psychotic symptoms after stressful events.

Although the existence of DPS is not yet proven beyond doubt, it has become an issue of growing importance in practice. Some studies suggest that people who reduce medication, or quit altogether, have a higher risk of relapsing into psychosis in the first years (possibly due to the now ‘supersensitive’ D2 receptor). Yet on the longer term (when the ‘supersensitive’ receptor has returned to normal), they are better off than people who remain on their regular high dose.

Many psychiatrists are still unfamiliar with DPS

It is important to recognise DPS in an early stage. Otherwise people can end up with huge doses of antipsychotics, while still only highly increasing the risk of psychosis. The antipsychotic clozapine might provide a solution. This type doesn’t ‘stick’ to the D2 receptor as strongly, thus allowing the receptor to rest and recover. The result: lower psychosis vulnerability and less abnormal body movements. Animal test studies show that the so-called ‘dopamine receptor partial agonists’ also have a lower risk of DPS.

Conclusion: antipsychotics and dopamine

The perspectives on antipsychotics are rapidly changing. Anyone using antipsychotics, should in any case take the risk of DPS into account. Doctors prescribing antipsychotics should do the same. From the very first start of using antipsychotics, an accompanying strategy is required for reducing the dosage to its minimum, out of concern for the physical health and the effects on the brain. Sound alternatives are dopamine receptor partial agonists or clozapine.

Psychological approaches aimed at learning how to deal with psychotic episodes should also be used much more in practice. Helping people find their way back to work and school – perhaps at an adjusted level when necessary – is probably the best medicine: being a part of the social world is healing for the brain and the mind.