One of the main features of schizophrenia is its unpredictability. It can develop according to various scenarios, which are quite difficult to predict. It is connected with the absence of exact knowledge about the reasons for psychopathology and various types of its manifestation. Resistant schizophrenia is observed in cases when the patient continues to have positive and negative symptoms even during remission. Why does this happen, and what do doctors do in such situations?


Resistant Schizophrenia


General information

According to medical statistics, about 5-30% of patients with schizophrenia are resistant to drug therapy. Simply put, they are partially or completely unaffected by medications that help most patients with similar diagnoses.

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

The typical scenario for the development of schizophrenia is as follows. The person begins to show symptoms such as apathy, depression, lack of interest and inability to enjoy himself. He withdraws into himself, engages in some mystical cults, and ceases to communicate, bathe and take care of themselves.

At any moment, he may have an attack (aggravation) during which his psyche is active, causing positive symptoms such as increased activity (often senseless), delusions, hallucinations, catatonic syndrome, etc.

See Also: Remission in schizophrenia

The speed of the course of schizophrenia depends on the form. Sometimes it develops for years almost asymptomatically. In these cases, a passive or latent type of psychopathology is detected. Some types progress rapidly, causing disintegration of the personality in just a year or several years.

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

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

Resistant schizophrenia differs in many ways from the classic scenario. During remission, a person exhibits both positive and negative signs. At the same time, medications that may have helped before do not have 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 is, the more serious the schizophrenic defect. There is no such dependence on drug resistance. But there is a connection between the early manifestation of the 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 genesis. But they can study the brain of an already sick person with the help of functional methods of research and neuroimaging.

They have shown that schizophrenia is closely linked to the work of transmitters, or neurotransmitters – biologically active substances that provide connections between neurons. These include serotonin, noradrenaline, dopamine, etc. People with schizophrenic disorders have impaired 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, delirium or fall into catatonic agitation. During the negative phase, the dopamine level is greatly reduced, accompanied by symptoms reminiscent of depression.

When treating schizophrenia, different kinds of antipsychotics are used to normalise neurotransmitters’ production. For hallucinations, neuroleptics that suppress the increased release of dopamine are prescribed, and during apathy, antidepressants are used. There are many such medications, but their principle of action is approximately the same. The doctor’s task is to choose the right drug and decide on the dosage.



As with the causes of schizophrenia, the factors that cause the body to become resistant to drugs are not yet exactly known. But physicians offer several versions of the development of resistance:

  • Weakness of standard medications.
  • The presence of side effects that prevent increasing the dose.
  • Prolonged intake of neuroleptics in a low dosage.
  • Failure to follow the doctor’s recommendations the patient.
  • Improperly diagnosed.

Psychiatrists G.Y. Avrutsky and A.A. Neduva distinguish several groups of patients who have developed a resistant type of schizophrenia. The first group includes patients whose resistance to medication is due to clinical factors. In such cases, curative is poorly predictable, in principle. Despite all the therapies, the patient’s condition does not improve.

Resistance due to clinical factors is found in 3% of people with schizophrenia.

The second group comprises 16.3% of patients and is simultaneously characterized by drug resistance due to therapeutic and clinical factors. First, we are talking about the moderate progredient nature of the pathological process. The patient manages to bring the patient into remission, but the symptoms actualize due to bad social and rehabilitative influences.

See Also: Schizophrenia and Drugs

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

Patients (about 41.6% of cases) with pseudo-resistance are most often observed. As a rule, the drugs work for them, but they are either chosen incorrectly or prescribed in the wrong dosage. But there are also patients (12.1%) who have more than one disorder. Sometimes doctors fail to treat the main symptoms even during the active phase.

In other words, the resistance issue in psychiatry is more than relevant. If it appears, it is necessary to ensure that it is not pseudo-resistance. Once it can be excluded, other causes of drug resistance are sought. The next step is to develop a new treatment regimen, including other drugs.



Resistance can be dynamic or static. The latter is characterized by a lack of early drug response and an unfavourable prognosis. But in the vast majority of cases, the first type occurs when initially the drug helped but subsequently stopped having an effect.

For this reason, experts recommend distinguishing three types of resistance:

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

Counting should be done not from the first signs but at the beginning of treatment with specific drugs.



In general, the symptoms of schizophrenia are determined by 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 flowing, seizure-like, etc.

These types differ from each other in the nature and intensity of symptoms. In case of resistance, those signs characteristic of the form of the disease detected in the patient will dominate. The criteria for determining drug resistance help determine the future treatment plan. These include:

  • Symptoms of the disease persist for an extended period.
  • Adverse course with frequent exacerbations.
  • Presence of active symptoms during remission.
  • Severe side effects of therapy.

Any of these criteria may cast doubt on the medications used in treatment.



It is important to mention here the fact related to lack of treatment compliance when the patient does not comply with the recommendations received from the doctor. A similar picture is observed in 50% of people with schizophrenia after their discharge from the hospital. In this case, we are talking about rejecting the doctor’s orders almost instantly. Another 25% add to this statistic within two years after leaving the hospital.

Often, in 50-80% of cases, such behaviour by patients is due to a lack of understanding of their condition. They consider themselves healthy and believe they will not allow the disease to progress again. But it progresses not because of moral weakness but because of unknown to science neurobiological mechanisms, which are still impossible to describe. That is why one must follow all the doctor’s recommendations.

It should be understood by the patients and their relatives, whose task is to support their loved ones in further treatment. This treatment is usually lifelong. A psychotherapist on this issue will consult the schizophrenic’s environment.


Psychoactive drugs

Another cause of therapeutic resistance is the schizophrenic’s drug or alcohol use. Three problems are possible in this context. First, it is more difan ficult to diagnose when someone with alcohol or drug abuse shows schizophrenia. It can be incorrectly diagnosed because of conflicting symptoms.

Second, people with schizophrenia have a preference for psychoactive substances. Often they try to eliminate the negative symptoms of schizophrenia with alcohol and drugs, which increases the risk of developing another exacerbation. The exact link 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 people with schizophrenia with addictions is steadily increasing.

Can pose the question of drug resistance about 4 to 8 weeks after starting medication.

Third, psychoactive substances affect neurotransmitters directly or indirectly. Drugs increase dopamine levels, which gives a person intense pleasure.

Alcohol, on the other hand, suppresses dopamine blockers, causing it to spike and raise the mood. Antipsychotics also affect neurotransmitters. Because of alcohol and drugs, medications may not have the desired effect.


Side effects

Antipsychotics are strong substances that are not available without a prescription. It is partly due to the high likelihood of side effects. They will be fewer if your doctor prescribes the right dosage. But it is difficult to predict how your body will react to a particular drug. Possible side effects include:

  • Neurological: dyskinesia (sudden involuntary muscle movements) and neuroleptic parkinsonism (spontaneous motor activity, muscle stiffness, tremor, wobbly gait).
  • Malignant neuroleptic syndrome: dystonia, rigidity, tachycardia, delirium, increased body temperature and other symptoms.
  • Seizure syndrome: epileptic seizures, registered in 0.5-0.9% of patients receiving antipsychotics.
  • Increased body weight: people with schizophrenia, in principle, are more likely to suffer from obesity due to unhealthy lifestyles, smoking and improper diet. The medication also contributes to this, contributing to weight gain.
  • Sexual dysfunction: the connection between sexual problems and antipsychotics has not yet been found. However, some patients report several problems in this area after the start of therapy.
  • Cardiovascular: tachycardia, myocarditis, and possible heart attack due to metabolic disorders.

Other side effects are also possible, including skin, gastrointestinal tract and visual organs. The patient usually stays in the hospital for the first few weeks or months, so doctors may adjust the therapy if necessary.


Problem Solution

This problem has not yet been completely solved. Many factors complicate the treatment of resistant schizophrenia, so you must be guided by the specific case each time. However, this does not mean there are no general regimens for such cases.

To date, clozapine, an antipsychotic from the neuroleptic group, has shown fairly high effectiveness. Doctors believe that it is the only way to overcome therapeutic drug resistance.

Unfortunately, clozapine is not suitable for all patients. Some do not respond to it as well as other medications. It leads to the need to divide all patients with resistant schizophrenia into two groups:

  • Clozapine-sensitive;
  • Clozapine-insensitive.

If clozapine does not work, then electroconvulsive therapy (ECT) is an option. ECT involves passing an electric current through the patient’s brain, causing the patient to have a seizure. This procedure is indicated for such factors as drug intolerance and resistance.

Between 40 and 70% with resistant schizophrenia do not respond to clozapine.

However, this technique cannot be considered salvageable either. First, it is used only in extreme cases, for example, when there is a high risk of suicide and severe depression. Secondly, it is not the fact that it will help to lead the patient to a relatively normal emotional state. A panel of physicians is up for discussion on whether or not it is appropriate to prescribe ECT.



In the most severe cases, when all methods fail, the patient is institutionalized. Treatment of resistant schizophrenia is a long-term process that cannot be temporarily abandoned and restarted again. An even greater set of symptoms usually accompanies each new episode.

If doctors have succeeded in stopping the main symptoms and bringing the patient into remission, they must do everything to prolong it. It will help to avoid serious damage to the personality. Otherwise, a complete disintegration of the personality is possible when the patient stops perceiving the world around him and becomes indifferent and apathetic.