Antipsychotics or neuroleptics are the psychoactive drugs used for the treatment of psychotic problems such as schizophrenia, although sometimes they also have other therapeutic indications.

There are a large number of them, with different properties and active principles in spite of having similar mechanisms of action. One of them is ziprasidone , which we will see throughout this article.

What is ziprasidone?

Ziprasidone is an antipsychotic or neuroleptic drug, classified within the atypical or second generation neuroleptics . This last clarification is necessary since it allows us to know that it will act not on dopamine but also on serotonin, in such a way that the levels of the former are altered only to the extent necessary in different brain areas.

In the main problem for which it is used, schizophrenia, there are excessive levels of dopamine in the mesolimbic pathway that end up causing symptoms such as hallucinations, excitability, and disorganized and erratic behavior. It is therefore necessary to reduce these levels, which is what all antipsychotics generate.

However, the former or typical ones generated many side effects or even impaired other types of symptoms present in some cases of schizophrenia , such as alogia or poor thinking, withdrawal or cognitive difficulties. This was because the action of classical antipsychotics was not specific to the mesolimbic pathway but occurs throughout the brain.

Thus, areas that were not altered in this way or that had deficient levels of dopamine such as the mesocortical pathway (this being the cause of negative symptoms such as alogia) are affected. For this reason, research continued and atypical antipsychotics were developed, including ziprasidone.

Mechanism of action

As an atypical antipsychotic, the mechanism of action of ziprasidone is based on the blockade of dopamine D2 receptors and a large part of the serotonin receptors (5HT2A, 5HT1A and 5HT2C), acting as an antagonist to them. Its effect on serotoninergic receptors is greater than that of other drugs such as risperidone . It also has an antagonistic effect, although much less so, on histamine and adrenaline. This means that ziprasidone acts in a way that makes it difficult for these hormones to be used by our neurons.

In the mesolimbic pathway, excess dopamine that generates positive symptoms (in the sense that it adds elements to the subject’s behavior), such as hallucinations and delusions, is reduced.

Although this drug has the same effect on the entire brain as it does on the mesolimbic pathway, the fact that it also acts as an antagonist to serotonin (which is an inhibitor of dopamine secretion), causes dopamine levels in other areas to be maintained or even increased in some places such as the cortex. This generates that there are less side effects and that there can be an improvement of the negative symptomatology (being the poverty of thought one of the most characteristic), which is linked to low levels of dopamine at a mesocortical level.

What is this psychopharmaceutical used for?

There are different disorders in which the use of ziprasidone can generate beneficial effects . Among these different applications and indications we can find the following.

Schizophrenia and other psychotic disorders

The best known and most frequent indication for ziprasidone is that corresponding to schizophrenia and other psychotic disorders , being effective in reducing positive symptoms and also having an effect on negative ones while generating fewer secondary symptoms than typical antipsychotics.

Bipolar disorder

Another indication for ziprasidone is for the treatment of bipolar disorder, specifically manic episodes in bipolar disorder type I. This medication allows for the reduction of manic symptoms such as hyperactivity, distractibility, feelings of grandeur , aggression or agitation.

Side effects and risks

Like all psychopharmaceuticals, ziprasidone, while effective, can generate a number of unpleasant side effects and potential risks.

As with other antipsychotics, ziprasidone can generate symptoms such as abdominal pain, fever, edema, hypersensitivity to light, hypothermia, hypertension, tachycardia, increased cholesterol, weight gain, nausea and vomiting, some extrapyramidal motor symptoms such as tardive dyskinesia and tremors, pneumonia. Sedation is another common secondary symptom, along with weakness and dizziness .

It can also generate sexual symptoms such as erectile dysfunction, menstrual disorders, gynecomastia, galactorrhea, delusions, walking problems, lack of coordination, anemia, jaundice, arrhythmias and heart problems. In some cases it may be necessary to go to medical services immediately, such as in the presence of convulsions, falls, priapism, loss of consciousness, muscular rigidity or arrhythmias.

Another risk to take into account is shared with all antipsychotics: the possibility of suffering from a neuroleptic malignant syndrome that can end with the patient’s death. Although the risks of this problem appearing are low, they must be controlled, and it is essential to control the doses that are prescribed and given to the patient (a process always supervised by doctors).


Ziprasidone is a potent and very effective drug that cannot be used at all times or on all types of people because it poses a possible health risk. It is contraindicated in people who have suffered some type of heart problem or disorder . Also in those elderly people who suffer from dementia, as it increases the risk of death.

Special care should be taken with interactions with other medications, as well as alcohol consumption. It is also not recommended for use in patients with diabetes, liver or kidney problems, people with epilepsy or seizures, breast cancer or spinal cord/blood problems. Finally, it is also not recommended during pregnancy or breastfeeding. In case of pregnancy, the doctor must be consulted about the possibility of changing the type of medication.

Comparison with other antipsychotics

As we have seen, there are numerous antipsychotics, and comparisons have been made between them to check their effectiveness.

In some studies and systematic reviews, it has been found that although highly effective, ziprasidone appears to be slightly less effective than other atypical antipsychotics such as olanzapine or risperidone. However, it has also been shown to be less likely to cause side effects .

Specifically, the subjects analyzed had a lower tendency to gain weight with medication and less tendency to raise cholesterol. Although compared to olanzapine it generated more probability of extrapyramidal symptoms and in relation to quetiapine an increase in prolactin (and therefore a greater number of sexual symptoms), in both cases it produced a lower level of these symptoms compared to risperidone. However, the research found that the abandonment of the studies by the participants meant that these data could be biased.

Bibliographic references

  • Komossa, K.; Rummel-Kluge, C.; Hunger, H.; Schwarz, S.; Bhoopathi, P.S.; Kissling, W. & Leucht, S. (2009). Ziprasidone vs other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews, 4. Art. No.: CD006627. DOI: 10.1002/14651858.CD006627.pub2.
  • Salazar, M.; Peralta, C.; Pastor, J. (2006). Manual of Psychopharmacology. Madrid, Editorial Médica Panamericana.