From the Editor

10 devastating consequences of psychotic relapses

Author and Disclosure Information



It breaks my heart every time young patients with functional disability and a history of several psychotic episodes are referred to me. It makes me wonder why they weren’t protected from a lifetime of disability with the use of one of the FDA-approved long-acting injectable (LAI) antipsychotics right after discharge from their initial hospitalization for first-episode psychosis (FEP).

Two decades ago, psychiatric research discovered that psychotic episodes are neurotoxic and neurodegenerative, with grave consequences for the brain if they recur. Although many clinicians are aware of the high rate of nonadherence in patients with schizophrenia—which inevitably leads to a psychotic relapse—the vast majority (>99%, in my estimate) never prescribe an LAI after the FEP to guarantee full adherence and protect the patient’s brain from further atrophy due to relapses. The overall rate of LAI antipsychotic use is astonishingly low (approximately 10%), despite the neurologic malignancy of psychotic episodes. Further, LAIs are most often used after a patient has experienced multiple psychotic episodes, at which point the patient has already lost a significant amount of brain tissue and has already descended into a life of permanent disability.

Oral antipsychotics have the same efficacy as their LAI counterparts, and certainly should be used initially in the hospital during FEP to ascertain the absence of an allergic reaction after initial exposure, and to establish tolerability. Inpatient nurses are experts at making sure a reluctant patient actually swallows the pills and does not cheek them to spit them out later. So patients who have had FEP do improve with oral medications in the hospital, but all bets are off that those patients will regularly ingest tablets every day after discharge. Studies show patients have a high rate of nonadherence within days or weeks after leaving the hospital for FEP.1 This leads to repetitive psychotic relapses and rehospitalizations, with dire consequences for young patients with schizophrenia—a very serious brain disorder that had been labeled “the worst disease of mankind”2 in the era before studies showed LAI second-generation antipsychotics for FEP had remarkable rates of relapse prevention and recovery.3,4

Psychiatrists should approach FEP the same way oncologists approach cancer when it is diagnosed as Stage 1. Oncologists immediately take action to prevent the recurrence of the patient’s cancer with chemotherapy and/or radiation therapy, and do not wait for the cancer to advance to Stage 4, with widespread metastasis, before administering these potentially life-saving therapies (despite their toxic adverse effects). In schizophrenia, functional disability is the equivalent of Stage 4 cancer and should be aggressively prevented by using LAIs at the time of initial diagnosis, which is Stage 1 schizophrenia. Knowing the grave consequences of psychotic relapses, there is no logical reason whatsoever not to switch patients who have had FEP to an LAI before they are discharged from the hospital. A well-known study by a UCLA research group that compared patients who had FEP and were assigned to oral vs LAI antipsychotics at the time of discharge reported a stunning difference at the end of 1 year: a 650% higher relapse rate among the oral medication group compared with the LAI group!5 In light of such a massive difference, wouldn’t psychiatrists want to treat their sons or daughters with an LAI antipsychotic right after FEP? I certainly would, and I have always believed in treating every patient like a family member.

Catastrophic consequences

This lack of early intervention with LAI antipsychotics following FEP is the main reason schizophrenia is associated with poor clinical and functional outcomes. Patients are prescribed pills that they often take erratically or not at all, and end up relapsing repeatedly, with multiple catastrophic consequences, such as:

1. Brain tissue loss. Until recently, psychiatry did not know that psychosis destroys gray and white matter in the brain and causes progressive brain atrophy with every psychotic relapse.6,7 The neurotoxicity of psychosis is attributed to 2 destructive processes: neuro­inflammation8,9 and free radicals.10 Approximately 11 cc of brain tissue is lost during FEP and with every subsequent relapse.6 Simple math shows that after 3 to 5 relapses, patients’ brains will shrink by 35 cc to 60 cc. No wonder recurrent psychoses lead to a life of permanent disability. As I have said in a past editorial,11 just as cardiologists do everything they can to prevent a second myocardial infarction (“heart attack”), psychiatrists must do the same to prevent a second psychotic episode (“brain attack”).

2. Treatment resistance. With each psychotic episode, the low antipsychotic dose that worked well in FEP is no longer enough and must be increased. The neurodegenerative effects of psychosis implies that the brain structure changes with each episode. Higher and higher doses become necessary with every psychotic recurrence, and studies show that approximately 1 in 8 patients may stop responding altogether after a psychotic relapse.12

Continue to: Disability


Next Article: