Chronic leukocytosis associated with clozapine treatment.

Clozapine is an important second-generation antipsychotic that is reserved for patients with refractory schizophrenia. Unfortunately, clozapine is also associated with a number of adverse effects, with agranulocytosis being one of the chief concerns. Interestingly, patients who receive clozapine treatment may occasionally experience elevations in their total white blood cell count (WBC). In some of these patients, the leukocytosis may be persistent. We report the case of a patient with refractory schizophrenia who is treated with clozapine and who experienced chronic leukocytosis. A brief review of the literature addressing clozapine-associated leukocytosis follows the case report.

The safety and efficacy of methylphenidate and dexmethylphenidate in adults with attention deficit/hyperactivity disorder.

OBJECTIVE: To review the literature on the safety and efficacy of methylphenidate, OROS-methylphenidate, methylphenidate ER, and dexmethylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). To analyze the effects of different doses of methylphenidate, it's various formulations, and methylphenidate on efficacy and safety in this population. DATA SOURCES: Literature retrieval was performed through Pubmed/MEDLINE (Up to May 2010) using the terms methylphenidate, dexmethylphenidate, and attention-deficit hyperactivity disorder. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: Double-blinded, placebo-controlled clinical trials, as well as crossover and open-label trials found using the search criteria listed above were included for review. Case reports were not included in this review. DATA SYNTHESIS: Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition that is commonly seen in children and adolescents, that persists into adulthood for about 50% of patients. Methylphenidate and dexmethylphenidate are often prescribed to treat the symptoms associated with ADHD. The literature validating the safety and efficacy of methylphenidate and dexmethylphenidate in children and adolescents with ADHD is substantial. However, the literature specifically addressing the safety and efficacy of these medications in the adult population is less extensive and prescribing is often anecdotal based on child and adolescent data. Understanding the literature regarding methylphenidate and dexmethylphenidate and its effects in adults can enhance evidence-based medicine (EBM) and improve treatment outcomes. CONCLUSION: Methylphenidate and dexmethylphenidate are safe and effective medications to treat the symptoms of ADHD in adults. Based on the literature, increased doses are associated with better treatment response with moderate safety concerns. The different dosage forms available enable individualization of treatment.

An update on central nervous system stimulant formulations in children and adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: To review recent literature on the different stimulant preparations regarding efficacy and safety in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and describe advantages and disadvantages of the many available dosage formulations. DATA SOURCES: Literature retrieval was performed through PubMed/MEDLINE (2005-December 2008) using the terms methylphenidate, amphetamines, central nervous system stimulants, and attention-deficit/hyperactivity disorder. In addition, reference citations from publications identified were reviewed and drug manufacturers were contacted for any possible additional references. STUDY SELECTION AND DATA EXTRACTION: Double-blind clinical trials found using the search criteria listed above were included for review. Open-label studies and studies prior to 2005 were included if no double-blind trials were published for that formulation within the time period reviewed. DATA SYNTHESIS: The literature reviewed here demonstrates the efficacy and safety of stimulant medications in children and adolescents with ADHD. However, there are 19 different formulations of stimulants, leading to confusion and errors in prescribing and dispensing of these drugs. Knowing and understanding the advantages and disadvantages of the different formulations can lead to individualized treatment. Formulations like Concerta, Focalin-XR, Adderall-XR, and Vyvanse provide the convenience of once-daily dosing. Each of these provides varying amount of stimulants at different times of the day. Vyvanse has a unique delivery system that may lower the risk of patients abusing their medication. Daytrana gives patients more control over their dosing by being able to choose when the patch is removed; it is also a feasible alternative for children who cannot swallow pills. For patients who cannot swallow tablets or capsules, the capsules of Focalin-XR, Adderall-XR, Metadate-CD, and Ritalin-LA can be opened and sprinkled on applesauce. CONCLUSIONS: Stimulants are effective medications to treat the symptoms of ADHD. The multiple available dosage forms allow for individualization of treatment.

Desvenlafaxine: another "me too" drug?

OBJECTIVE: To compare desvenlafaxine with its parent drug, venlafaxine, to determine the usefulness of this new medication. DATA SOURCES: Information was obtained through a MEDLINE search (1966-June 2008) and from published abstracts. Search terms included desvenlafaxine, O-desmethylvenlafaxine, Pristiq, major depressive disorder, and venlafaxine. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and abstracts pertaining to desvenlafaxine and venlafaxine were considered for inclusion. Preference was given to human data. DATA SYNTHESIS: Desvenlafaxine is a serotonin-norepinephrine reuptake inhibitor and is the active metabolite of the antidepressant venlafaxine. The recommended dose is 50 mg daily, based on the efficacy and safety data of 50, 100, 150, 200, and 400 mg of desvenlafaxine. The response and remission rates of depression at 8 weeks for the 50-mg dose are 51-63% and 31-45%, respectively. These rates are comparable with those seen with venlafaxine (58% and 45%, respectively). Adverse effects are also similar to those of venlafaxine, with the most common being insomnia, somnolence, dizziness, and nausea. The decreased potential of CYP2D6 activity with desvenlafaxine compared with the parent drug may be a potential advantage in patients on other medications metabolized via this enzymatic pathway. Also, desvenlafaxine tablets are less expensive than extended-release (XR) venlafaxine, which may decrease healthcare costs in the short term. However, venlafaxine XR is expected to go off patent in 2010. CONCLUSIONS: With the overall similarity between these 2 drugs and the potential lack of cost savings, the need for desvenlafaxine and its ultimate utility in treating major depressive disorder appears to be insignificant.

Atypical antipsychotics in children with pervasive developmental disorders.

The treatment of pervasive developmental disorders (PDDs) is a challenging task, which should include behavioral therapy modifications as well as pharmacologic therapy. There has been a lack of data on using medications in children with PDDs until recent years. Within the last 10 years, an increase in clinical research has attempted to provide efficacy and safety data to support the use of medications in children with PDDs. Double-blinded and open-label research of atypical antipsychotics has been of particular focus. Evidence shows that atypical antipsychotics (AAs) may be useful in treating certain symptoms associated with PDDs, such as aggression, irritability, and self-injurious behavior. This article reviews the literature regarding the use of AAs in children with PDDs. Of the AAs, risperidone has the largest amount of evidence with five published double-blinded, placebo-controlled trials and nine open-label trials. These risperidone trials have consistently shown improvements in aggression, irritability, self-injurious behavior, temper tantrums, and quickly changing moods associated with autistic disorder and other PDDs. Data for the other AAs are limited, but ziprasidone and aripiprazole appear to be promising treatment options. Based on clinical trials, olanzapine and quetiapine have shown minimal clinical benefit and a high incidence of weight gain and sedation. It should be noted that all AAs do have a risk of metabolic syndrome, and patients should be monitored appropriately while receiving these medications. Overall, AAs can be beneficial in alleviating behavioral symptoms, and should be considered an appropriate therapeutic option, as part of a comprehensive treatment strategy, for children with PDD.