Concepts of Schizophrenia Treatment

Everyone has heard the term schizophrenia. Around this disorder, numerous myths and misunderstandings have accumulated over the centuries. Since ancient times, people experiencing psychotic disorders were treated either as madmen—excluded from society—or as saints—also excluded from society, albeit for different reasons.

Attempts to treat schizophrenia date back to the Middle Ages, when various methods were employed in an effort to restore individuals to “normality.” A wide range of therapeutic approaches were used, among which physical punishment and torture were disturbingly popular—the more elaborate, the better.

Until relatively recently, treatment through forced labour was also common. Even toward the end of the twentieth century, agricultural hospital facilities were still being closed.

The Evolution of Schizophrenia Concepts

With the development of scientific research methods, new concepts of schizophrenia began to emerge.

These ranged from the theory of the “schizophrenogenic mother”—which unjustly blamed mothers for their children’s illness—through psychoanalytic interpretations, to environmental, stress-related, viral, genetic, and immunological theories.

There are dozens of conceptual models of schizophrenia.

Fortunately, it became evident that schizophrenia is a disorder that can be treated by means other than branding with hot iron or exorcisms.

What Is Schizophrenia?

The challenge of defining schizophrenia was aptly described by Professor Henry A. Nasrallah, who compared it to scientists describing an elephant while blindfolded.

One researcher touches the tail and concludes the elephant is a rope.
Another touches the trunk and believes it is a pipe.
A third touches the side and declares it a wall.

Similarly, schizophrenia is a complex phenomenon perceived differently depending on the angle of observation.

Schizophrenia is currently understood as a neurodevelopmental disorder, in which pathological symptoms emerge over time.

If left untreated, it may lead to early-onset dementia, as Emil Kraepelin accurately described when he coined the term dementia praecox.

Advances in Understanding

Today, we are increasingly closer to understanding schizophrenia as a biological and neurofunctional disorder.

We can identify:

• structural and functional brain changes

• alterations at the neuronal level

• abnormalities in receptors and neurotransmitter systems

We now know that neurons in schizophrenia function differently:

• they produce altered amounts of neurotransmitters

• receptor activity is dysregulated

Traditional Treatment Approaches

Historically, treatment focused on:

• blocking postsynaptic receptors

• modulating presynaptic mechanisms

However, neurons are not passive. When postsynaptic receptors are blocked, neurons compensate by producing additional receptors, which leads to adverse effects such as:

• akathisia

• tremors

• hyperprolactinaemia

As a result, many patients developed strong resistance to first-generation antipsychotics.

Classic drugs such as chlorpromazine, fluphenazine, and promazine were associated with significant side effects. One notable exception was clozapine, which demonstrated a unique ability to induce remission. Its effect was long attributed to its broad receptor-binding profile.

Today we know that this unique effect is largely due to its influence on intracellular TAAR1 receptors, enabling modulation of neurotransmitter release.

Second- and Third-Generation Antipsychotics

Second-generation antipsychotics—such as risperidone and olanzapine—offered improved tolerability and fewer side effects.

The third generation, including aripiprazole, brexpiprazole, and cariprazine, consists of partial receptor agonists, functioning fundamentally differently from earlier medications.

Emerging Therapeutic Strategies

Current research focuses on entirely new classes of compounds acting on:

• peptide receptors

• trace amine-associated receptors (TAAR 1–3)

These agents modulate the presynaptic neuron itself across multiple neurotransmitter systems. Their effects may be:

• direct

• indirect, via activation of other neurotransmitter pathways that subsequently regulate neuronal function associated with schizophrenic symptoms

Additionally, promising effects have been observed with agents acting on muscarinic M1 and M4 receptors, leading to significant symptom improvement.

Clinical Effects of Novel Treatments

Based on current observations, the use of investigational next-generation agents results in:

• resolution of delusions and hallucinations (positive symptoms)

• substantial improvement in negative symptoms

Patients exhibit:

• reduced apathy and social withdrawal

• renewed interest in social interaction

• return to hobbies and personal interests

• improved cognitive functions, including memory and concentration

• reduction of dementia-like symptoms

Patients re-engage with external reality, symptoms resolve, and they begin functioning comparably to healthy individuals.

Future Outlook

Provided that no significant adverse effects emerge, we may soon be able to treat psychotic disorders effectively while focusing on the development of therapies capable of permanently curing schizophrenia.

The trajectory of modern psychopharmacology suggests a future in which remission is no longer the ultimate goal—complete recovery may become achievable.