Typical and Atypical Antipsychotics

Typical and Atypical Antipsychotics: Schizophrenia

Drug therapies are the biological side of treatment for schizophrenia. Typical antipsychotics (also known as neuroleptics), mostly, if not entirely, address the positive symptoms of schizophrenia, such as hallucinations and paranoia. They also reduce the impact of these symptoms in general.

With the development of atypical antipsychotics, negative symptoms such as avolition can also be addressed.

Positive symptoms of schizophrenia, such as delusions, are due to the increased release of dopamine in the brain. This in turn increases the activation of dopamine 2 receptors (D2) (Brisch et al., 2014) and can result in the aforementioned positive symptoms, as dopamine acts as a modulator for many brain functions. Similarly, negative symptoms can develop when there is reduced function of dopamine receptors in the prefrontal cortex.

Psychologists classify antipsychotics into two categories: typical and atypical.

What are Typical Antipsychotics?

Typical antipsychotics are the first generation of drug therapies available for schizophrenia. They were developed in the 1950s, and have lost popularity since the advent of atypical antipsychotics for several reasons. Most notably due to the notion that typical antipsychotics cause more severe side effects than atypical antipsychotics.

Typical Antipsychotic Examples

Typical antipsychotic drug examples include:

• Chlorpromazine

• Haloperidol

• Pimozide

• Loxapine

They work by blocking the dopamine 2 receptor (D2), reducing the uptake of dopamine in the mesolimbic pathway (also known as the reward pathway), and can differ in potency. Positive symptoms are a result of the increased subcortical release of dopamine in the brain, possibly due to a defect in the cortical pathway through the nucleus accumbens (Brisch et al., 2014). By blocking the D2 receptors and effectively calming the dopamine system in the brain, typical antipsychotics lower the intensity of positive symptoms.

Fig. 2 - Overview of reward structures in the human brain, including the mesolimbic pathway, commons.wikimedia.org

Due to the calming effect, there tends to be a general sedative effect too. Like many drugs, typical antipsychotics come with a list of unintended side effects.

Common Side effects of Typical Antipsychotic

Some of the side-effects include, but are not limited to:

• Dry mouth.

• Constipation.

• Low energy.

• Sedation.

• Tardive dyskinesia (uncontrollable muscle movements usually affecting the face).

• Akathisia (uncomfortable restlessness).

There is no explicit evidence to state one typical antipsychotic drug is more or less effective than another. This tends to be decided by a patient’s reaction and feelings towards the effectiveness of the drug, and how they tolerate it.

What are Atypical Antipsychotics?

Atypical antipsychotics are considered the second generation of antipsychotic drug treatments. Developed in the 1970s, they avoid the more severe side effects of typical antipsychotics.

Atypical Antipsychotic Examples

Atypical antipsychotic drugs include:

• Clozapine

• Olanzapine

• Risperidone

• Quetiapine

They work somewhat similarly to typical antipsychotics in that they block D2 dopamine receptors in the limbic system. However, they do not affect dopamine receptors in other parts of the brain. The reduction of intensity in positive symptoms occurs as a result, but they also act on other neurotransmitters, notably:

• Acetylcholine

• Glutamate

• Serotonin

Common Side Effects of Atypical Antipsychotic

Like typical antipsychotics, atypical antipsychotic drugs come with their list of unintended side effects:

• Cardiovascular problems.

• Weight gain.

• Drowsiness.

• Diabetes.

• Tardive dyskinesia (uncontrollable muscle movements usually affecting the face). This is less likely to happen with atypical antipsychotics.

Although atypical antipsychotics are referred to as second-generation antipsychotics, there’s an increasing amount of research going into the efficacy of atypical antipsychotics in the treatment of schizophrenia.

Difference Between Typical and Atypical Antipsychotics

Now that we have established typical and atypical antipsychotics, we can highlight the differences between typical and atypical antipsychotics.

Consider the antipsychotic drug comparison chart. Here, we can see:

• Typical antipsychotics are first-generation drugs, and atypical antipsychotics are considered to be second-generation drugs.
• Typical antipsychotics were developed in the 1950s, whereas atypical antipsychotics were developed in the 1970s.
• Typical antipsychotics treat positive symptoms of schizophrenia, whereas atypical antipsychotics address both positive and negative symptoms of schizophrenia.
• Typical antipsychotics work by blocking dopamine 2 (D2) receptors, whereas atypical antipsychotics work by blocking some but not all dopamine receptors, unlike typical antipsychotics, and affect other neurotransmitters such as serotonin and glutamate.
• Typical antipsychotics calm the dopamine system in the brain, acting as dopamine antagonists, whereas atypical antipsychotics calm the dopamine and other systems in the brain, and are also known as serotonin-dopamine antagonists.
• Side effects differ. Typical antipsychotics are said to have harsher side effects.

List of Typical and Atypical Antipsychotics

To summarise the content discussed above, here is a list of typical and atypical antipsychotics. Typical antipsychotics include:

• Chlorpromazine

• Haloperidol

• Pimozide

• Loxapine

Atypical antipsychotics include:

• Clozapine

• Olanzapine

• Risperidone

• Quetiapine

Are Antipsychotic Drug Therapies Effective and Appropriate in Treating Schizophrenia?

Now that we know what typical and atypical antipsychotics are, we now must establish through evaluation whether or not they are effective and appropriate for treating schizophrenia.

Strengths of Antipsychotic Drugs

Let's consider some of the strengths of using biological treatments for schizophrenia.

• Leucht et al. (2013) reviewed 212 studies, testing the effectiveness of biological antipsychotic drug treatments on how they normalise dopamine levels. 15 antipsychotic drugs were compared to their controls (placebo) in the acute treatment of schizophrenia. They were significantly more effective than the placebo, so treatments targeting dopamine are effective in reducing symptoms. They also disagreed with the current classification of typical and atypical antipsychotics, suggesting a hierarchy would be more suitable.

• Drug therapies are often cheaper than hospital treatments, and therapies such as cognitive behavioural therapy (CBT), and family therapy. Psychological therapies require weeks of sessions with a trained professional.

• Due to drug treatments, there are fewer long-term institutionalised patients in mental health hospitals. As a result of this independence from clinical, in-house treatments, patients lead a more independent lifestyle and are in general happier and more fulfilled.

• Schooler et al. (2005) found that, when comparing haloperidol (typical antipsychotic) to risperidone (atypical antipsychotic), low doses of antipsychotic drugs were able to significantly improve symptoms of psychosis associated with schizophrenia in first-episode patients (those early in the course of psychotic/schizophrenic illness or treatment). In the long-term, risperidone has lower rates of relapse and induces fewer abnormal movements (tardive dyskinesia) than haloperidol. This shows that antipsychotics are effective in treating positive and negative symptoms of schizophrenia. However, there were issues with dropouts in treatments.

• Bagnall et al. (2003) analysed 232 studies comparing the effectiveness of atypical and typical antipsychotics. Overall, atypical antipsychotics were more effective in treating the symptoms of schizophrenia, with fewer movement disorder side effects. Fewer people also left the drug treatment early, a problem in most studies. Clozapine was the most effective at reducing negative symptoms and treating those resistant to other drugs. This suggests antipsychotics are effective treatments, especially those focused on more neurotransmitters than dopamine.

• Crossley et al. (2010) found that, although there were no true differences between the efficacy of first and second-generation antipsychotics, second-generation were shown to cause fewer side effects in the patients.

Weaknesses of Antipsychotic Drugs

Let's consider some of the weaknesses of using biological treatments for schizophrenia.

• Lieberman et al. (2005) compared the first-generation, typical antipsychotic drug perphenazine to a selection of second-generation, atypical drugs, such as olanzapine amongst 1,493 patients with schizophrenia. It was found that only olanzapine outperformed perphenazine in terms of discontinuation rates (where patients stop taking their medication). The rest did no better than the perphenazine.

  • Although olanzapine had superior efficacy in reducing psychopathology compared to the rest, it also had more severe side effects, such as significant weight gain.

• Kahn et al. (2008) compared first-generation haloperidol with second-generation antipsychotics. 498 patients were randomly assigned an antipsychotic treatment plan. Kahn found that antipsychotics were effective for at least one year, however, they could not conclude that second-generation antipsychotics were more effective than first-generation antipsychotics, as discontinuation rates were not synonymous with symptom improvement.

• The amount of research indicating no true difference in the efficacy of first-generation and second-generation antipsychotics in treating schizophrenia calls into question the need to make this distinction at all, again raising concerns over the classification of typical and atypical antipsychotic drugs.

• The side effects of antipsychotic drugs are quite severe. Overall, two-thirds of people with schizophrenia stop taking their medication. This creates an issue with the revolving door of treatment plans. This is where patients take their antipsychotics, find their symptoms are not being treated effectively, or are not worth the severe side effects such as tardive dyskinesia and significant weight gain, and stop taking them before eventually resuming treatment again later on because symptoms are becoming problematic again.

• Repeated treatment plans also create issues with forced treatment. If the symptoms a patient is experiencing are severe to the point of significant distress, drugs may often be prescribed forcefully. This is an ethical issue, as informed consent is compromised, especially considering the severity of the side effects.

• Drug therapies are also only suppressing the symptoms of schizophrenia, and not treating the root cause.

It is worth noting that Tarrier et al. (1998) placed patients in a combined treatment plan of antipsychotics and CBT. These patients had a significant improvement in the severity and number of their positive symptoms. So, a combination of therapies as treatments is worth considering and will be explored in the next explanations on this topic.