Clozapine is a medication used for treatment-resistant schizophrenia and sometimes treatment-resistant bipolar disorder. It is classified as an atypical or second generation antipsychotic [SGA] medication. These medications work like the older medications for schizophrenia by blocking a neurotransmitter called dopamine, but also by targeting the neurotransmitter serotonin. Clozapine is unusual in that it targets dopamine less than any of the other antipsychotic medications. In fact, clozapine targets numerous other neurotransmitters making it a unique compound with the highest level of efficacy in treating schizophrenia. Clozapine does also come with required lab monitoring to prevent rare but serious lab abnormalities.
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Answered by:
Donna Rolin, PhD, APRN, SMI Nursing Expert - University of Texas,
Austin
Date Answered: June 5, 2019
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Schizophrenia is a complicated mental illness that can be hard to treat. Antipsychotic drugs greatly improve symptoms for many people. But about a third of those with the condition have what’s called treatment-resistant schizophrenia [TRS]. Doctors consider
schizophrenia treatment-resistant if: Even if you don’t get better with traditional antipsychotics, there’s treatment that may help. You may be a candidate for clozapine [Clozaril, Versacloz], a so-called second-generation antipsychotic drug that often works for this condition. Studies show that those with TRS are more likely than others with schizophrenia to have: Clozapine is the only FDA-approved medication for treatment-resistant schizophrenia. It treats symptoms of psychosis like hallucinations and
delusions. It also improves mood and behavior. You take it as a tablet or liquid. It works by rebalancing levels of dopamine and other chemicals in your
brain. If it works for you, it can be life-changing. It makes a major difference in your quality of life, reduces the chances that you’ll be hospitalized, and greatly reduces your risk of suicide. But clozapine isn’t effective for 50%-60% of people with TRS. They can have active psychosis even with daily doses for up to 6 months. Clozapine
also may have side effects including: It can also cause a serious side effect that decreases the number of white blood cells you
have, making you more prone to infections. You can’t feel this, so you’ll need weekly blood tests to make sure you don’t get it. After you’ve been taking clozapine for a while, you may need those tests only every few weeks.Who’s at Risk for Treatment-Resistant Schizophrenia?
How Is Treatment-Resistant Schizophrenia Treated?
Other serious potential side effects include: Your doctor will probably start you on a low dose, and increase it gradually. When your doctor prescribes clozapine: It
can also be a challenge for your doctor to know if clozapine is right for you. Sometimes it takes up to a year to know whether it’s working properly. And there are few other medications for TRS. If clozapine isn’t working well after 6 months, your doctor may: They may add another antipsychotic drug to the mix, such as risperidone [Risperdal] or aripiprazole [Abilify].
Some experts say that because of the blood tests and the possible side effects, doctors tend to under-prescribe clozapine. But delayed treatment may make it less likely that the drug will work for you.
When Clozapine Doesn’t Work
For TRS, there aren’t many well-tested treatments besides clozapine. But if you don’t respond well to it, your doctor could try adding electroconvulsive therapy [ECT] to your treatment plan.
In ECT, a doctor uses a device to pass mild electric currents through your brain, triggering a short seizure. This causes brain chemistry changes that can relieve symptoms of some mental illnesses. We need more research, but some studies found that ECT combined with clozapine helped control symptoms of psychosis.
If that’s not effective, your doctor might try adding other drugs, including:
- Lamotrigine, an anti-seizure medicine
- Topiramate, also a seizure medication
- Minocycline, an antibiotic with anti-inflammatory properties
But we also need more research into how well these drugs might work for TRS.
Your doctor could also try repetitive transcranial magnetic stimulation [rTMS] along with your clozapine treatment. In rTMS, doctors use an electromagnet to deliver repeated magnetic pulses that stimulate nerve cells in your brain. It’s not clear how effective it is for TRS, though.
Like most people with schizophrenia, those with TRS can likely benefit from psychotherapies such as cognitive behavioral therapy [CBT]. This kind of therapy can help people with schizophrenia:
- Understand and manage their symptoms
- Improve their life and social skills
- Lower their risk of suicide attempts
There’s not much research into psychotherapy for treatment-resistant schizophrenia in particular. But some studies have shown that it may be helpful for certain symptoms.