Categories: Psychotherapy
      Date: Jan 26, 2010
     Title: New Developments in the Maintenance Treatment of Schizophrenia Part II

Second generation (atypical) antipsychotics represent another revolution in the care of schizophrenia patients. These medications include clozapine, risperidone, olanzapine, quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify), and paliperidone (Invega). They are antagonists of
the dopamine type 2 and serotonin 2A receptors.
As a group they have differences, but share several common actions, including the treatment of negative symptoms, less extrapyramidal symptoms (which may improve compliance), and a tendency toward less tardive dyskinesia. On the down side, second generation antipsychotics as a class can cause metabolic syndrome, which includes dyslipidemia, abdominal obesity, elevated blood pressure, a proinflammatory state with elevations of C-reactive protein, and a prothrombotic state (Grundy et al.).
All these medications carry a warning about their use in elderly demented patients. Oral paliperidone is a metabolite of risperidone and as such has a similar mechanism of action—blocking dopamine D2 and serotonin HT2 receptors. It also has a blocking effect on adrenergic alpha 1 and alpha
2 as well as histamine 1 receptors. It is contained in a hardened container that has a semipermeable membrane and as such has a controlled, sustained osmotic-driven release over time.
Overall, these medications have led to significant improvement in the quality of life of many patients suffering from schizophrenia. Several atypical antipsychotics are available in wafer forms that
dissolve on contact with the tongue. These are felt to reduce the incidence of “cheeking”
medications and therefore may increase compliance. Risperidone has been available as a long-acting intramuscular injection for several years. Until recently, it was the only atypical available in a longacting
form. It usually is administered biweekly and requires oral medication to supplement it for several weeks after its initiation.The newest development in this form has been the introduction of paliperidone
palmitate (Invega Sustenna), now approved by the Food and Drug Administration for the acute and maintenance treatment of schizophrenia. It appears to have several significant advantages over the other atypical extended formulation such as the ability to administer the product monthly instead of
biweekly injections.
As the newest entry in the market, a closer look at the advantages of paliperidone palmitate is warranted. The drug is generally well tolerated and was found to be safe and effective in premarketing studies. Unlike the long-acting risperidone product, paliperidone palmitate does not require oral supplementation at treatment initiation. A long-term maintenance study (paliperidone vs. placebo) was terminated early for humanitarian reasons after analysis showed paliperidone was significantly more likely to delay the time to recurrence of symptoms. The usual starting dose for adults is an injection of 234 mg followed by another injection of 156 mg one week later. After that, the recommended monthly
dose is 117 mg. This medication actually achieves better serum levels with deltoid injections over gluteal injections. Since this is a new product, only extensive clinical experience will reveal its place in the therapeutic armamentarium for the treatment of schizophrenia, but for now it gives providers
another option for patients which have potentially critical advantages.

References

Grundy SM, Brewer Jr. HB, Cleeman JI, Smith Jr SC, Lenfant MD. NHBLI/AHA Conference Proceedings: Definition of Metabolic Syndrome. Circulation 2004; 109:433-8.Hough D, Gopal S, Vijapaurkar U, et al. Paliperidone palmitate, an atypical injectable antipsychotic, inprevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study [poster]. Presented at American Psychiatric Association 161st Annual Meeting; Washington, DC; May 3-8, 2008.Hough D, Jindenmayer, J-P, Gopal S, et al. Safety and tolerability of deltoid and gluteal injections of paliperidone palmitate ini schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2009; 33:1022-31.
Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209-23. Olfson M, Mechanic D, Hansell S. Predicting medication noncompliance after hospital discharge among patients with schizophrenia. Psychiatric Services 2000; 51:216-22.
Rainer MK. Risperdone long-acting injection: a review of its long term safety and efficacy. Neuropsychiatric disease and treatment 2008; 4:919-27.