The drugs for schizophrenia used primarily for treatment are antipsychotic or neuroleptic drugs. Like all psychoactive drugs, when ingested, antipsychotics produce specific modifications in the brain.
Specifically, they tend to act on dopamine , serotonin and histamine. The main chemical activity of antipsychotics lies in blocking the receptors of different neurotransmitters. In this way, they reduce the level of brain excitement.
This factor explains the efficacy of these drugs in reducing typical symptoms of psychosis such as delusions and hallucinations. By reducing the amount of active neurotransmitters in the brain, positive symptoms are reduced.
However, not all types of antipsychotics have the same characteristics or have the same effects on the brain. Specifically, today we find two main types of neuroleptics: typical antipsychotics and atypical antipsychotics.
Typical antipsychotics, also known as first-generation antipsychotics or conventional antipsychotics, are a class of neuroleptic drugs that were developed in the middle of the last century.
They were designed for the treatment of psychoses, especially schizophrenia, although they can also be suitable drugs to intervene in manic episodes, agitation or other types of emotional disturbances.
Within the classic antipsychotics, two types of drugs can be distinguished: low- potency neuroleptics and high-potential neuroleptics.
The first group is made up of chlorpromazine, promethazine, thyidazine, and mildomepromazine. The second includes fluephenazine, haloperidol, trifluoperazine, and pimozide.
-How do they work?
The mechanism of action of these drugs is based on four different pathways: the mesocortical pathway, the mesolimbic pathway, the nigrostriatal pathway, and the tuberoinfundibular pathway.
The mesocortical pathway is associated with neurocognitive symptoms and disorders in the modulation of emotions and affectivity. Classic antipsychotics block this pathway, so their consumption can cause negative effects such as apathy, affective flattening or neurocognitive deterioration.
The mesolimbic pathway, for its part, is involved in the pathophysiology of the positive symptoms (delusions and hallucinations) of schizophrenia.
Classical antipsychotics block dopamine receptors, a fact that allows the excess of this substance to be reduced in the brain, and reduces psychotic symptoms.
Classic antipsychotics block dopamine (D2) receptors in the nigrostriatal pathway. This factor is strongly associated with an increased risk of experiencing extrapyramidal symptoms such as muscle stiffness, poor balance, or loss of control in movements.
Dopamine acts as an inhibitory factor for prolactin. Thus, the blocking of D2 receptors by typical antipsychotics facilitates their release in the pituitary gland.
-Types of typical antipsychotics
Due to the side effects that classic antipsychotics cause and that they only serve to treat the positive symptoms of schizophrenia (and not the negative ones), the use of these drugs has clearly been surpassed by atypical antipsychotics.
However, these drugs are still used today. In fact, eight different types of classic antipsychotic drugs are available on the market. These are:
Fluphenazine is an antipsychotic drug that comes as a tablet or liquid to take by mouth. It is usually taken two or three times a day.
It is a little used medicine today due to its side effects. The main ones are: upset stomach, drowsiness, weakness or tiredness, anxiety, insomnia, nightmares, dry mouth, sun- sensitive skin and appetite alterations.
This medicine comes in tablet form and is usually taken once or twice a day. It is mainly used to treat the symptoms of schizophrenia and occasionally to intervene episodes of anxiety.
The side effects of this drug are also numerous. Its consumption can cause drowsiness, dizziness, blurred vision, dry mouth, nasal congestion, nausea, difficulties urinating, constipation, changes in appetite, difficulties sleeping, headaches, weakness or extreme fatigue among others.
Mesoridazine is used to treat schizophrenia, agitation, anxiety, tension, hyperactivity, and lack of cooperation. It can be consumed both in tablets and in liquid form.
Liquid concentrate must be diluted before consumption. Likewise, due to the stomach upset caused by the drug, it is usually recommended to take it with food or milk.
Its consumption can cause drowsiness, vomiting, diarrhea, constipation, headache, weight gain and agitation.
It is a classic low-potency antipsychotic, and it was one of the most widely used medications in the treatment of schizophrenia symptoms during the past century.
Today its consumption is much lower due to its side effects and the low efficacy it presents to intervene the negative symptoms of the disease.
However, several people with schizophrenia are still treated with chlorpromazine today.
It is another low potency antipsychotic drug. It has been used for many years as a treatment for the positive symptoms of schizophrenia.
However, this drug can cause a type of severe heartbeat irregularity. Fact that can even cause sudden death.
For this reason, its use as an antipsychotic drug is currently discouraged, since there are other effective drugs that have fewer risk factors.
Haloperidol is the best-known classical antipsychotic drug, and the drug that has been used most widely for the treatment of schizophrenia. In fact, until the advent of atypical antipsychotics, haloperidol was the main drug for the treatment of psychotic disorders.
It can be taken both through tablets and by injection, and works to decrease abnormal arousal in the brain. Apart from schizophrenia, it is also used to treat serious behavioral problems, such as aggressive and explosive behavior or hyperactivity.
It is one of the most powerful antipsychotics, but its consumption can cause side effects such as blurred vision, loss of appetite, constipation, heartburn, lack of expression on the face, uncontrollable movements in the eyes, mood changes or decreased sexual capacity.
Thiothixene comes in capsule form. It is used to treat symptoms of schizophrenia, but unlike other drugs, the Food and Drug Administration (FDA) has not approved its use for the treatment of behavior problems.
Likewise, this drug is not recommended as a treatment in people with demential syndromes, since it increases the probability of death.
This drug has strong similarities with thiothixene. It is used to treat the symptoms of schizophrenia but it is not recommended to intervene in behavioral disorders and dementia syndromes.
Likewise, the use of molindone is remarkably limited today due to its side effects.
Drowsiness, increased salivation, difficulties urinating, lack of expression on the face, depression, changes in menstruation and sexual desire, and decreased ability to walk are the most important.
Finally, loxapine is a typical antipsychotic that was previously used to treat the positive symptoms of schizophrenia.
However, the long list of side effects caused by its consumption, and the ineffectiveness in treating the negative symptoms of the disease mean that this drug is practically not used today.
Atypical or new generation antipsychotics are antipsychotic medications that present certain differences from the typical ones. These differences make them better therapeutic options for treating schizophrenia.
-How do they work?
Atypical antipsychotics, unlike typical antipsychotics, specifically inhibit D2 receptors. In this way, they have a lower propensity to produce extrapyramidal symptoms.
Atypical antipsychotics have the advantage of not producing an increase in prolactin secretion, a fact that is present with the administration of conventional antipsychotics.
Atypical antipsychotics, unlike typical antipsychotics, also block serotonin receptors. For this reason, they are more effective in controlling the negative symptoms of schizophrenia.
New antipsychotics have been shown to be effective in patients who do not respond correctly to treatment with conventional antipsychotics.
For this reason, these drugs are the most commonly used today. Both to intervene the symptoms of schizophrenia (positive and negative) and to treat episodes of anxiety, agitation or hyperactivity.
-Types of atypical antipsychotics
The efficacy of these drugs in treating the two types of schizophrenia symptoms has led to a clear preference for atypical antipsychotics over classic antipsychotics.
Likewise, the reduction of extrapyramidal effects, one of the main disadvantages of antipsychotics, has also contributed to increasing scientific interest in these drugs.
In this sense, research on atypical antipsychotics is booming, these drugs are being used more and more and today they are vital to intervene in schizophrenia.
Currently, there are five main types of atypical antipsychotics that are used very frequently. These are:
Clozapine was the first atypical antipsychotic drug to be developed. In fact, its design revealed the efficacy of the mechanism of action and the effects of this type of drug, a fact that uncovered interest in these new antipsychotics.
It was created at the end of the 50s of the previous century and its main characteristics were: a low rate of extrapyramidal neurological adverse effects and greater efficacy compared to typical antipsychotics in the treatment of schizophrenia.
However, clozapine also has significant adverse effects. Its consumption can cause strong sedation, weight gain, a decrease in blood pressure and an increase in triglycerides in the blood.
Thus, clozapine is currently a second-choice drug due to its toxicity and the side effects it presents.
Its main indications lie in the treatment of subjects with schizophrenia who do not respond to other atypical antipsychotics, and individuals with schizophrenia who present severe extrapyramidal symptoms.
Apart from schizophrenia, it can also be used to treat delusional disorders, severe manic and depressive episodes, and diseases such as Parkinson’s and Lewy Body Dementia that present with delusions or hallucinations.
Risperidone is another of the highly used atypical antipsychotics today. It is sold commercially as Risperdal and is frequently used as a treatment for schizophrenia.
Likewise, the Food and Drug Administration (FDA) has also authorized its use to intervene in bipolar disorder, autistic disorders, panic attacks, obsessive-compulsive disorder, Tourette’s syndrome and severe depression.
However, its consumption can cause side effects such as weight gain, dyskinesia, akathisia, lack of energy, sexual dysfunction, retrograde ejaculation, anxiety or insomnia.
Olanzapine is a widely used drug for the treatment of schizophrenia, bipolar disorder, and severe depressive episodes.
Structurally it closely resembles clozapine, although it has a higher affinity for serotonin receptors than for dopamine receptors.
Likewise, unlike most antipsychotics, olanzapine has a higher affinity for histamine and muscarinic receptors.
It is considered one of the most effective antipsychotic drugs, although its consumption also causes side effects such as weight gain, impotence or insomnia.
Finally, quetiapine is an atypical neuroleptic that is marketed under the name Seroquel. It is used to treat schizophrenia and bipolar disorders.
It is highly effective in the treatment of these diseases, which is why it has been established as one of the first choice drugs. Likewise, it has the advantage of causing a limited range of side effects.
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