How Effective Are the Newest Antipsychotics? [Free Article]

Four new antipsychotics are beginning to gain some traction in the adult market. To be absolutely clear, among these only paliperidone (Invega) has been approved for use in children and adolescents (those age 12 and older). None of the other medications have been tested in this age group. But for those of us who see transitional age youth to whom we prescribe antipsychotics, here is a quick low down on paliperidone, iloperidone (Fanapt), lurasidone (Latuda), and asenapine (Saphris).

Paliperidone (Invega) is the oldest of the set, and is the active metabolite of risperidone (Risperdal). It has been touted as having fewer side effects than risperidone, but it seems to have outlived its honeymoon period: the literature abounds with case reports of the usual trouble-makers (weight gain, sedation, hyperprolactinemia) and serious side effects (dystonia, tardive dyskinesia, neuroleptic malignant syndrome). Thus, it appears to have much the same effect—both for better and for worse—as risperidone. The good news is that any patient who has been on risperidone in the past has already been exposed to paliperidone, so it’s reasonably safe (as safe as risperidone), though much more expensive than its mother compound

Asenapine causes some drug interaction mischief. It is metabolized by CYP 1A2, and so is subject to CYP1A2 inhibitors like fluvoxamine (Luvox). In addition, it inhibits CYP2D6, and can thus increase the serum levels of drugs metabolized by that system, such as paroxetine (Paxil).

Like lurasidone, asenapine seems to cause fewer metabolic problems than other atypicals. On the downside, it frequently causes sedation and akathisia (but less EPS than haloperidol), and infrequent elevations in prolactin. It also causes oral numbing in 4% of patients. Weight gain is primarily a problem in relatively skinny patients (BMI less than 23). Mild QTC prolongation occurs, but a more frequent cardiac side effect is reflex bradycardia (slow heart rate) with sinus pause. Although benign and self-limiting, this could easily frighten a patient. Efficacy studies were sufficient for FDA approval, but overall are unimpressive, with no increased efficacy over comparator drugs, and some studies failed to find a difference from placebo (Citrome L, Int J Clin Pract 2009;63(12):1762–1784).