One of the main features of schizophrenia is its unpredictability. It can develop according to a variety of scenarios, which are quite difficult to predict. This is due to the lack of precise knowledge about the causes of psychopathology and the many forms of its manifestation. Resistant schizophrenia occurs when the patient has positive and negative symptoms even during remission. Why does this happen and what do doctors do in such situations?

Resistant Schizophrenia

General Information on Resistant Schizophrenia

According to medical statistics, about 5-30% of patients with schizophrenia have resistance to drug therapy. To put it simply, they are partially or completely not affected by drugs that help most patients with similar diagnoses.

Resistant schizophrenia is permanent and chronic. In general, any form of this disorder other than hypochondriasis is incurable. The patient is diagnosed for life. However, in most cases, the disease proceeds in the form of alternating attacks and remissions, during which positive and negative signs are observed, respectively.

A typical scenario for the development of schizophrenia is as follows. The person begins to develop symptoms such as apathy, depression, lack of interest, and inability to enjoy. He withdraws into himself, begins to get involved in some mystical cults, and stops communicating, washing, and taking care of himself.

At any moment, he can have an attack (exacerbation), during which the psyche is active, which causes the appearance of positive symptoms – increased activity (often meaningless), delusions, hallucinations, catatonic syndrome, etc.

The rate of progression of schizophrenia depends on the form. Sometimes it develops for years almost asymptomatically. In such cases, a sluggish or latent type of psychopathology is revealed. Some of its types progress rapidly, causing the disintegration of the personality in just a year or a few years.

But almost always, first negative symptoms are observed, then productive ones, and during the period of remission, residual signs are characteristic of the passive phase.

Many scientists are inclined to believe that schizophrenia is an umbrella diagnosis that combines many types of diseases.

Resistant schizophrenia differs in many ways from the classical scenario. During the remission period, a person has both positive and negative signs. At the same time, drugs that could help before do not give any effect.

Moreover, resistant schizophrenia differs from the usual forms in that it does not depend on the duration of the psychosis. As a rule, the longer it lasts, the more serious the schizophrenic defect. With drug resistance, there is no such dependence. But there is a connection between the early manifestation of pathology and subsequent resistance.


Neurotransmitter Theory

As noted earlier, the causes of schizophrenia are unknown. We are talking about the etiology and pathogenesis of the disease. Scientists have not yet been able to study the mechanism of its origin. But they can examine the brain of an already ill person using functional research methods and neuroimaging.

They showed that schizophrenia is closely related to the work of transmitters, or neurotransmitters – biologically active substances that provide connections between neurons. Among them are serotonin, norepinephrine, dopamine, etc. In people with schizophrenic disorders, there is a violation of the production of neurotransmitters.

During the active phase, a person releases a lot of dopamine. It binds to receptors in the brain, which gives the body too many commands. During such periods, patients see hallucinations, delusions,s or fall into catatonic excitement. During the negative phase, dopamine levels are significantly reduced, which is accompanied by symptoms resembling depression.

In the treatment of schizophrenia, various kinds of antipsychotic substances are used that normalize the production of neurotransmitters. With hallucinations, antipsychotics are prescribed that suppress the increased release of dopamine, and during a period of apathy, antidepressants are used. There are a lot of types of such drugs, but the principle of their action is approximately the same. The task of the doctor is to choose the right drug and determine the dosage.


Causes for Resistant Schizophrenia

As with the causes of schizophrenia, the factors that cause drug resistance in the body are not yet known exactly. But doctors offer several versions of the development of resistance:

  • Weak action of standard drugs.
  • The presence of side effects that do not allow to increase in the dose.
  • Long-term use of neuroleptics in low dosage.
  • Non-compliance with the recommendations of the doctor by the patient.
  • Wrong diagnosis.

Psychiatrists G.Ya. Avrutsky and A.A. Neduva distinguishes several groups of patients who have developed a resistant form of schizophrenia. The first includes patients whose drug resistance is due to clinical factors. In such cases, curability (curability) is poorly predicted, in principle. Despite all the means of therapy, the patient’s condition does not improve.

Resistance due to clinical factors is detected in 3% of schizophrenics.

The second group is 16.3% of patients, characterized by drug resistance due to both therapeutic and clinical factors. We are talking, first of all, about the moderate progression of the pathological process. The patient can be brought into a state of remission, but due to the lack of social and rehabilitation impact, the symptoms are updated.

Therapeutic factors cause resistance to the third type, which includes 12.6% of patients. In such cases, the body simply adapts to a particular drug and stops responding to it. Initially, they give an effect, but later become useless.

Most often, patients are observed (in approximately 41.6% of cases) with pseudo-resistance. As a rule, drugs act on them, but they are either chosen incorrectly or prescribed in the wrong dosage. But there are also such patients (12.1%) who have several disorders. Sometimes doctors fail to stop the main symptoms even in the active phase.

In other words, the issue of resistance in psychiatry is more than relevant. If it appears, you need to make sure that this is not a pseudo-resistance. Once it has been ruled out, other causes of drug resistance are being sought. The next step is to develop a new treatment regimen with the inclusion of other drugs.


Treatment of Resistant Schizophrenia

Here it is important to mention the fact associated with the lack of adherence to treatment when the patient does not follow the recommendations received from the doctor. A similar picture is observed in 50% of schizophrenics after their discharge from the hospital. In this case, we are talking about an almost instantaneous refusal of the doctor’s prescriptions. Another 25% replenish these statistics within two years after leaving the clinic.

Often, that is, in 50-80% of cases, such behavior of patients is due to a lack of understanding of their condition. They consider themselves healthy and believe that they will not allow the recurrence of the disease. But it progresses not because of moral weakness, but because of neurobiological mechanisms unknown to science, which cannot yet be described. For this reason, you need to follow all the recommendations of the doctor.

This should be understood by both the patients themselves and their relatives, whose task is to support their loved ones in the subsequent treatment. It is usually for life. On this subject, the environment of a schizophrenic is consulted by a psychotherapist.


Psychoactive Substances

Another reason for therapeutic resistance is the use of drugs or alcohol by a schizophrenic. There are three problems in this context. First, when a person with alcoholism or drug addiction shows signs of schizophrenia, it is more difficult to make a diagnosis. It may be installed incorrectly due to conflicting symptoms.

Secondly, schizophrenics have an addiction to psychoactive substances. Often they try to eliminate the negative symptoms of schizophrenia with the help of alcohol and drugs, which increases the risk of developing another exacerbation. The exact relationship between alcohol or drugs, on the one hand, and schizophrenic disorders, on the other, has not been established. However, statistics show that the number of schizophrenics with addictions is constantly growing.

The question of drug resistance can be raised approximately 4-8 weeks after the start of their use.

Thirdly, psychoactive substances act directly or indirectly on neurotransmitters. Drugs simply increase the level of dopamine, which brings a person a lot of pleasure.

Alcohol, on the other hand, suppresses dopamine blockers, causing it to surge and elevate mood. Antipsychotics also act on neurotransmitters. Because of alcohol and drugs, drugs may simply not work.


Types of Resistant Schizophrenia Over Time

Resistance is dynamic and static. The latter is characterized by a lack of early response to drugs and a poor prognosis. But in the vast majority of cases, the first type occurs, when the medicine initially helped, but subsequently ceased to have an effect.

In this regard, experts recommend distinguishing three variants of resistance:

  • Early – in the first year of therapy;
  • Medium – within 1-5 years;
  • Late – 5 years after the start of admission.

The countdown should not be from the first signs, but from the start of treatment with specific drugs.


Signs of Resistant Schizophrenia

In general, the signs of schizophrenia are due to its type and form. The main types are paranoid, catatonic, hebephrenic, and simple. According to the variant of the course, the disorder is divided into sluggish, malignant, continuously current, paroxysmal (coat-like), etc.

These varieties differ from each other in the nature and intensity of symptoms. With resistance, those signs that are characteristic of the form of the disease identified in the patient will dominate. Criteria for determining drug resistance help determine the further treatment plan. Among them:

  • Symptoms of the disease persist for a long time.
  • Unfavorable course with frequent exacerbations.
  • Presence of active symptoms during remission.
  • Severe side effects of therapy.

The presence of any of these criteria may call into question the drugs used in the treatment.


Side effects

Antipsychotic drugs are strong substances that are not available without a prescription. This is partly due to the high likelihood of side effects. They will be less if the doctor correctly prescribes the dosage. But it is difficult to predict exactly how the body will react to a particular drug. Possible side effects include:

  • Neurological: dyskinesia (suddenly occurring involuntary movements in the muscles) and neuroleptic parkinsonism (spontaneous motor activity, muscle stiffness, tremor, unsteady gait).
  • Malignant neuroleptic syndrome: dystonia, rigidity, tachycardia, delirium, fever, and other symptoms.
  • Convulsive syndrome: epileptic seizures, which are recorded in 0.5-0.9% of patients receiving antipsychotics.
  • Weight gain: Schizophrenics are generally more likely to become obese due to unhealthy lifestyles, smoking, and poor diet. Medications also contribute to this, contributing to mass gain.
  • Sexual dysfunction: A link between sexual problems and antipsychotics has not yet been found. However, some patients report a number of problems in this area after the start of therapy.
  • Cardiovascular: tachycardia, myocarditis, and the possibility of a heart attack, as a result of metabolic disorders.

Other side effects are possible, including in the skin, gastrointestinal tract, and organs of vision. In the first weeks or months, the patient, as a rule, is in the hospital, so doctors can, if necessary, adjust the treatment regimen.



In the most severe cases, when no methods help, the patient is left in the hospital. The treatment of resistant schizophrenia is a long process that cannot be abandoned temporarily and then started over again. Each new attack, as a rule, is accompanied by an even greater set of symptoms.

If the doctors managed to stop the main symptoms and bring the patient into remission, everything must be done to prolong it. This will help to avoid serious damage to personal qualities. Otherwise, a complete disintegration of the personality is possible, when the patient ceases to perceive the world around him and becomes indifferent and indifferent.