Megan J. Ehret

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.

Assessment of Human Serotonin 1A Receptor Polymorphisms and SSRI Responsiveness

AbstractBackground: Depression is thought to involve, in part, dysregulation of serotonergic neurotransmission. In depressed individuals, the number of serotonin receptors, including the 5-hydroxytryptamine (serotonin)-1A (5-HT1A) autoreceptors, are increased. Clinical improvement with selective serotonin reuptake inhibitors (SSRIs) is not usually observed until several weeks after treatment initiation. This delay may be due to the time it takes for the autoreceptors to downregulate. Roughly one-third of patients with depression do not respond to an initial trial of antidepressant medication treatment, possibly as a result of structural variations in the 5-HT1A receptor. Aims: This study was designed to determine the allelic frequency of seven 5-HT1A receptor polymorphisms in a depressed versus a nondepressed population, and in SSRI responders versus nonresponders. All the polymorphisms studied are single nucleotide polymorphisms (SNPs) in the HTR1A gene, which encodes 5-HT1A. Seven prevalent SNPs were included in the analysis. Results: The study showed no relationship between any of the HTR1A polymorphisms and SSRI responders versus nonresponders. Conclusion: While the study has several limitations, the results are consistent with a growing body of literature that suggests that the pharmacogenetics of depression (an inherently complex disorder) may turn out to be multifactorial, and may include the HTR1A gene in concert with other serotonin-related genes.

Long-Acting Injectable Risperidone

OBJECTIVE To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of long-acting (LA) risperidone for the treatment of schizophrenia. DATA SOURCES Information was selected from PubMed (1965–July 2004). Applicable scientific posters were also used. STUDY SELECTION AND DATA EXTRACTION All published information on risperidone LA was considered. Material providing a comprehensive description was considered. DATA SYNTHESIS Risperidone LA is the first long-acting, injectable atypical antipsychotic. It is dosed at 25–50 mg every 2 weeks. Adverse effects are similar to those seen with oral risperidone. A short-term study showed that risperidone LA is better than placebo in reducing the signs and symptoms of schizophrenia, and a long-term trial showed that stable schizophrenic patients can be switched from either oral or other injectable antipsychotic medications to risperidone LA. CONCLUSIONS Risperidone LA is efficacious and safe in the treatment of schizophrenia.

The effect of metformin on anthropometrics and insulin resistance in patients receiving atypical antipsychotic agents: a meta-analysis.

CONTEXT In the Clinical Antipsychotic Trials of Intervention Effectiveness, atypical antipsychotics (AAPs) were found to be associated with weight gain and impairment of glucose metabolism. While metformin has been shown to attenuate weight gain and insulin resistance, not all studies have shown a benefit in the reduction of antipsychotic-induced weight gain and insulin resistance. OBJECTIVE To characterize metformins impact on anthropometrics and insulin resistance in patients taking AAPs. DATA SOURCES A systematic literature search of MEDLINE, EMBASE, and Cochrane CENTRAL was conducted from the earliest possible date through December 31, 2008. The search was performed using the following Medical Subject Headings and text keywords: metformin, biguanide(s), in combination with neuroleptic(s), neuroleptic drug(s), antipsychotic(s), dopamine antagonist(s), atypical antipsychotic(s), psychotropic(s), risperidone, olanzapine, quetiapine, ziprasidone, sulpiride, clozapine, iloperidone, aripiprazole, paliperidone, melperone, bifeprunox, amisulpride, zotepine, and sertindole. STUDY SELECTION Six of 62 identified studies (N = 336 participants) met our inclusion criteria: randomized, placebo-controlled trials of metformin in patients taking AAPs with data on weight, body mass index (BMI), waist circumference, insulin resistance (determined using the homeostasis model assessment of insulin resistance [HOMA-IR]), and/or a diagnosis of diabetes. DATA EXTRACTION Data were independently abstracted by 2 investigators; disagreements were resolved through discussion or by a third investigator using a standardized data abstraction tool. For continuous endpoints, the weighted mean difference (WMD) of the change from baseline with 95% CI was calculated as the difference between the mean in the metformin and placebo groups. For categorical endpoints, the pooled relative risk (RR) with 95% CI was calculated. A random-effects model was used for all analyses. DATA SYNTHESIS Compared to placebo, the metformin group had significantly reduced weight (WMD, 3.16 kg; P = .0002), BMI (WMD, 1.21 kg/m²; P = .0001), waist circumference (WMD, 1.99 cm; P = .005), and HOMA-IR (WMD, 1.71; P = .004). The reduction in risk of diabetes was not statistically significant (RR, 0.30; P = .13). CONCLUSIONS This analysis suggests that using metformin in patients treated with AAPs may reduce metabolic risks. Additional randomized controlled trials are needed, but available data support consideration of this intervention in clinical practice.

Current Practices in the Treatment of Alzheimer Disease: Where is the Evidence After the Phase III Trials?

PURPOSE The purpose of this systematic review was to review the current place in therapy of the 4 medications, donepezil, rivastigmine, galantamine, and memantine, approved for the treatment of Alzheimer disease (AD) since the publication of Phase III trials. METHODS A systematic literature search of MEDLINE and EMBASE was conducted for articles published in the past 10 years. The search was performed using the following Medical Subject Headings and text key words: Alzheimers disease, treatment, donepezil, galantamine, rivastigmine, memantine, dementia of the Alzheimers type, and dementia. FINDINGS Studies that evaluated new doses, indications, and dose formulations remain a large part of the current literature. Donepezil gained approval for the treatment of severe AD and became available in a 23-mg/d dose formulation. Rivastigmine became available in a patch formulation. Memantine became available as an extended-release capsule. Use of a combination product formulation was recently approved, memantine extended release/donepezil. Controversy among clinicians remains regarding when to initiate therapy, appropriate duration of therapy, and how and when to discontinue the treatment of AD. IMPLICATIONS Only drugs that affect cholinergic function have shown consistent, but modest, clinical effects, even in late-phase trials. There is a need for a better appreciation of the various risk factors and drug targets for the treatment of AD. The wide range of targets makes it unlikely that affecting only 1 of those targets (eg, cholinergic function or N-methyl-d-aspartate) will lead to a more than minimally effective treatment option, regardless of when a treatment is started and discontinued. There is substantial opportunity for the continued growth and development of drugs and clinical trial expansion for the treatment of AD.

Vilazodone: a novel antidepressant.

PURPOSE The pharmacology and pharmacokinetics of the antidepressant vilazodone (approved for U.S. marketing in 2011) are reviewed, with an emphasis on efficacy and safety data from Phase III clinical trials. SUMMARY Vilazodone (marketed as Viibryd by Forest Pharmaceuticals) is a dual-acting serotonergic agent that combines the antidepressant effects of a selective serotonin-reuptake inhibitor (SSRI) with partial serotonin (5-HT)(1A)-receptor agonist activity. In two published eight-week Phase III trials involving a total of 878 adults with major depressive disorder (MDD), vilazodone use was found to yield significant symptomatic improvements relative to placebo use, as determined by mean changes from baseline in scores on the Hamilton Depression Rating Scale and other widely used clinical assessment instruments. Vilazodone hydrochloride therapy should be initiated at a dosage of 10 mg once daily and incrementally adjusted over 14 days to the recommended target daily dose of 40 mg; for optimal bioavailability and effectiveness, it should be taken after a light or high-fat meal. The adverse effects most commonly reported in clinical trials of vilazodone were diarrhea, nausea, vomiting, and insomnia. CONCLUSION Vilazodone is an efficacious and safe new antidepressant for the treatment of MDD. Its relatively high cost and adverse-effect profile, as well as a lack of data demonstrating that vilazodone can produce long-term MDD remission and offer significant advantages over the current standard of care, may limit the usefulness of vilazodone in clinical practice.

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-desmethyIvenlafaxine, 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.

Prevention of interferon-alpha-associated depression with antidepressant medications in patients with hepatitis C virus: a systematic review and meta-analysis

To conduct a systematic review and meta‐analysis evaluating the efficacy and safety of antidepressant medications for the prevention of interferon‐alpha (INF‐α)‐associated depression in patients with chronic hepatitis C virus (HCV).

Long‐term Use of Atypical Antipsychotics in Bipolar Disorder

Bipolar disorder is a chronic disease that may require lifetime treatment. The maintenance therapy of bipolar disorder can be challenging for the treating clinician. Currently, according to the American Psychiatric Association (APA) guidelines, lithium, valproic acid, lamotrigine, carbamazepine, oxcarbazepine, and the antipsychotics are recommended for the maintenance treatment of bipolar disorder. The antipsychotics are recommended to be continued only if the clinician decides that they are necessary for the control of persistent psychosis or for prophylaxis against recurrence. Although the APA guidelines provide sufficient evidence for the use of these mood stabilizers, newer drugs such as the atypical antipsychotics are being investigated for use in the maintenance phase of treatment of bipolar disorder.

Psychotropic medication adherence in correctional facilities: a review of the literature.

Despite the high percentage of incarcerated persons with mental illness, surprisingly little is known about effective ways to increase psychotropic medication adherence in prison and upon release. Currently, there are limited definitive data regarding psychotropic medication adherence patterns among incarcerated persons, and the data that exist often miss specific information on changes in behaviour, symptom management and adherence patterns over the length of a persons sentence, which has implications for post-release ability to live in the community. This paper presents the current literature regarding psychotropic medication adherence among mentally ill persons who are incarcerated. The factors identified in support of medication adherence, future clinical research and care strategies are provided.