1 Boring Old Man

Time to discontinuation of first- and second-generation antipsychotic medications in the treatment of schizophrenia.
^{by Kreyenbuhl J, Slade EP, Medoff DR, Brown CH, Ehrenreich B, Afful J, Dixon LB.}
Schizophrenia Research. 2011 131(1-3):127-32.

^{BACKGROUND: Continuous adherence to antipsychotic treatment is critical for individuals with schizophrenia to benefit optimally, yet studies have shown rates of antipsychotic discontinuation to be high with few differences across medications. We investigated discontinuation of selected first- and second-generation antipsychotics among individuals with schizophrenia receiving usual care in a VA healthcare network in the U.S. mid-Atlantic region.
METHODS: We identified 2138 VA patients with schizophrenia who initiated antipsychotic treatment with one of five non-clozapine second-generation antipsychotics or either of the two most commonly prescribed first-generation agents between 1/2004 and 9/2006. The dependent variable was duration of continuous antipsychotic possession from the index prescription until the first gap of more than 45 days between prescriptions. We used the Cox proportional hazards model to compare the hazard of discontinuation among the seven antipsychotics controlling for patient demographic and clinical characteristics. The reference group was olanzapine.
RESULTS: The majority of patients (84%) discontinued their index antipsychotic during the follow-up period (up to 33 months). In multivariable analysis, only risperidone had a significantly greater hazard of discontinuation compared to olanzapine (Adjusted hazard ratio=1.15, 95% CI: 1.02-1.30, p=.025). Younger age, non-white race, homelessness, substance use disorder, recent inpatient mental health hospitalization, and prescription of another antipsychotic were also associated with earlier discontinuation.
CONCLUSIONS: Examination of a usual care sample of individuals with schizophrenia revealed short durations of antipsychotic use, with only risperidone having a shorter time to discontinuation than olanzapine. These findings demonstrate that current antipsychotic agents have limited overall acceptability by patients in usual care.}

^[C.A.T.I.E.]

^{[European Schizophrenia Study]}

^{Among an observational sample of VA patients with schizophrenia beginning a new episode of antipsychotic treatment, the overwhelming majority (84%) discontinued their medication during the study period. This finding is consistent with the CATIE Schizophrenia study (Lieberman et al., 2005), in which 74% of pati\ents discontinued antipsychotic treatment within 18 months, and supports the results of studies in similar usual care samples ( [Cooper et al., 2005] , [Mullins et al., 2008] and [Moisan and Grégoire, 2010] ). Although several studies document similarly high rates of antipsychotic discontinuation, it is striking that only 16% of patients who discontinued their index antipsychotic in this study had a prescription filled for a different antipsychotic agent within 45 days. This suggests that a majority of patients had an interruption in antipsychotic treatment which increased their risk for serious adverse outcomes. Taken together, these findings suggest that despite the introduction of several new antipsychotic medications over the past 15 years, available treatments may not address the needs and preferences of most individuals with schizophrenia.}

^{Although evidence-based treatment guidelines for schizophrenia recommend ongoing antipsychotic treatment for all patients and the risks of antipsychotic discontinuation can be considerable, it should not be assumed that every decision to interrupt treatment is necessarily irrational. For example, the decision to discontinue a treatment that is not providing adequate relief of target symptoms or whose side effect profile is intolerable and thus impeding rather than facilitating recovery may be a logical response, signaling the need for the patient and clinician to jointly consider an alternate treatment strategy…}

^{Contrary to our hypothesis, we found the median length of treatment for each of the SGAs and FGAs evaluated in this study to be generally similar to that of olanzapine. The only exception was risperidone, which demonstrated a statistically significantly greater risk of discontinuation compared to olanzapine, a finding that was observed in CATIE and some … but not all … previous observational studies. Our results add to the accumulating evidence that the effectiveness of olanzapine, and possibly aripiprazole and ziprasidone, may be superior in some ways to that of risperidone…}

^{Our results did not confirm earlier findings … of a greater risk of treatment discontinuation for quetiapine, nor did we observe any specific advantages for olanzapine over the two most recently introduced SGAs during the study period, ziprasidone and aripiprazole. In contrast to earlier research …, we also did not find evidence of a greater rate of discontinuation for the two most frequently prescribed FGAs, haloperidol and chlorpromazine, relative to olanzapine….}

^{I’ve had a lot of reactions through the years to this topic. I remember as a resident noting that my colleagues would get mad at the patients for discontinuing their "meds" and showing up with florid psychosis. I felt differently. I saw it as an impossible dilemma. No meds = psychosis. Meds? I once took a 1.0 mg Haldol pill. I felt like a tree [until I became Rip Van Winkle and slept for a day]. So it was tree versus psychotic. When anti-med people talk, I see an ocean of out of control psychotic hallucinating and delusional people that have passed my way over the years, and remember a visit to the old Central State Hospital [a horrid place]. When pro-med people speak, I remember my 1 mg Haldol experiment and cases of Tardive Dyskinesia. When I trained residents, if they ever did the disdainful "stopped meds" presentation, I made them go back and do the history over. I suggested they try my Haldol experiment [but they rarely took me up on it]. So I see the issue of anti-psychotic meds as always having two sides – neither great.}

^{I have no credentials to have an opinion, but I have one anyway. It’s that the psychotic aspects of Schizophrenia are not primary – that Schizophrenia itself is a more basic problem in understanding and processing meanings in the world. And that frank psychosis is a solution, but not the primary problem I don’t know how to describe the primary problem in intuition any better than I’ve already mentioned [1. from n equals one…].}

^{But I do know something to say about this paper. One reason the patients stop taking the medication is simple. They don’t want to take it. They don’t see it as treatment…}