Case debrief

The patient has later-onset schizophrenia. It was actually caught in his first psychotic break

After early remission of symptoms, he had a second break, which never truly remitted. He has continued with mild to moderate positive and mild negative symptoms throughout treatment

He tried typical antipsychotics, atypical antipsychotics, clozapine (Clozaril) without remission

He tried typical antipsychotics, atypical antipsychotics, clozapine (Clozaril) and developed EPS and TD

He tried typical antipsychotics, atypical antipsychotics, clozapine (Clozaril) and developed metabolic disorder

Finally, it was decided that his symptoms would likely be controllable but remain mild and that finding an agent with less EPS and metabolic side effects would be beneficial over the long term

Almost every atypical antipsychotic (except aripiprazole [Abilify]) was tried, but finally dosed on an atypical antipsychotic with low EPS and low metabolic risks (lurasidone [Latuda]), frankly as it was the most recently approved and released to the market at the time

At the time of this book going to press, he was also tried on the new liquid preparation of clozapine (Versacloz), and again at 200–300 mg/d, developed excessive drooling, which was unresponsive to scopolamine and glycopyrrolate augmentation

Given his previous TD and EKG changes, he is monitored closely

This patient was discovered later to have mild Wolf–Parkinson–White arrhythmia, which was ablated by cardiology. Upon retrial with Versacloz, he did not experience cardiac tachyarrhythmia side effects again, although his QTc did suffer a 20 ms elongation limiting the use of the clozapine product line

This patient has failed to respond to non-antipsychotic augmentation options: lamotrigine (Lamictal), minocycline (Minocin) [yes, the antibiotic], lithium carbonate

• – Interestingly, these ideas were obtained by attending a CME event where an expert panel discussed refractory schizophrenia cases

ECT may be considered

Despite his remaining symptoms, the patient works part-time as a store clerk and seems to be doing well psychosocially

There are flare-ups in his symptoms, which are often dealt with by changing his environment and utilizing family therapy and job counseling

He is maintained on the higher-potency typical antipsychotic trifluoperazine (Stelazine) at varying doses, on top of a low dose of clozapine

This strategy appears to keep psychosis from worsening and minimizes his EPS, and he has less need for anticholinergics and their associated side effects

Take-home points

This case emphasizes the need for full therapeutic trials of antipsychotic treatments

Many guidelines suggest aggressive monotherapies versus polypharmacy approaches

Use of approved medications at approved doses is warranted

However, in more treatment-resistant cases, doses above those approved may be warranted, if monitored reasonably

• – Sometimes, patients metabolize antipsychotics aggressively and blood levels may be low

• – Measuring therapeutic drug levels, if available, may allow super-dosing strategies that actually bring the patient to therapeutic levels

• – Obtaining therapeutic drug levels may increase the clinician’s confidence in dosing the antipsychotic to higher levels

Finally, much consideration should be given to the patient’s symptom severity, chronicity, and the ultimate side-effect burden as they will endure over a lifetime of treatment

Choosing a lower side effect burden agent is preferred when possible

• – There are 11 different atypical antipsychotics (12 with clozapine) in the United States and all with differing side-effect profiles

When side effects develop and must be endured, utilizing polypharmacy to reduce these side effects is often warranted

• – In this case, benztropine for EPS, metformin, and omega-3-acid ethyl esters for metabolic side effects were used