We’ve recently posted about some of the reasons aripiprazole and ziprasidone can make good choices for treatment.
Read about ziprasidone here.
This is an overview of the drug aripiprazole.
Spectrum of Efficacy
Aripiprazole has now been approved for acute and maintenance treatment of pediatric patients with bipolar disorder from ages 10 to 17. It had already been approved for adult bipolar disorder, schizophrenia, and as an adjunctive treatment for acute unipolar depression inadequately responsive to antidepressants of the serotonin-selective class or the serotonin-norepinephrine reuptake inhibitor venlafaxine. Aripiprazole, along with risperidone, is one of only two drugs FDA-approved for the treatment of irritability in autism.
Adding aripiprazole to the drug regimen of a patient with major depression was significantly superior to adding placebo on most of the core symptom items of major depression in a pooled analysis of several studies. Martin et al. presented these data in a poster at the American Psychiatric Association meeting in San Francisco in May 2009. The improved areas included: trouble falling asleep, feeling sad, low mood, decreased appetite, view of the self, view of the future, thoughts about death/suicide, general interest, capacity for pleasure/enjoyment, interest in sex, and interpersonal sensitivity.
These improvements were accompanied by improvements at a trend or significance level in quality of life after just six weeks of treatment, as well as a generally good side-effects tolerability profile. The most common side effects are akathisia (restless legs) and restlessness, which appear to be less prominent if one starts with very low (pediatric) doses, i.e. 1mg to 2mg/day. The metabolic profile of the drug is relatively benign, with only weight gain occurring significantly more on aripiprazole than on placebo, while there were no significant changes in cholesterol or triglycerides.
Ziprasidone has shown efficacy in pediatric BP I disorder (ages 10 to 17). Its metabolic profile is the most benign of the atypical antipsychotics, including being the only one that does not produce weight gain in children. None of the other metabolic indices increased either.
This drug is currently rarely used in children because of concerns about its effects on electrocardiogram (EKG), which have rarely been seen in clinical practice. Perhaps the overall assessment of its risk/benefit ratio should be re-evaluated.
We’ve posted before about ziprasidone’s benign side effects profile.
The two main classes of drugs for the treatment of Alzheimer’s disease currently include cholinesterase inhibitors, which increase brain acetylcholine levels, and memantine (Namenda), which is a partial blocker of glutamate receptors. Treating patients with both types of drugs in combination may help their cognitive functioning.
The brains of patients with Alzheimer’s are deficient in acetylcholine. Acetylcholinesterase breaks down acetylcholine, so the first class of Alzheimer’s drugs inhibits these esterases and makes more acetylcholine available.
Memantine works a different way. Glutamate is the major excitatory neurotransmitter in the brain. Excesses of glutamate may be toxic to cells, so memantine’s ability to partially block glutamate receptors may explain the drug’s effectiveness in Alzheimer’s.
In a study comparing valproate monotherapy with the combination of lamotrigine and divalproex (Valproate) extended release (ER), the combination appeared more effective in bipolar depression. At the American College of Neuropsychopharmacology meeting in December 2009, Vivek Singh, Charles Bowen, Richard Weisler, and colleagues from The University of California, San Diego reported on the randomized, double-blind, eight-month maintenance study of bipolar depressed patients.
Patients who could be stabilized for two consecutive weeks on the combination treatment of both lamotrigine and divalproex were then randomized to either lamotrigine alone or the combination for the duration of the study. Most of the data collected about these 87 subjects favored the treatment with the combination (lamotrigine plus divalproex) compared with lamotrigine alone. Combination therapy was superior for manic symptomatology and resulted in lower rates of unanticipated worsening of depression (greater than 20 points on the Montgomery-Asberg depression rating scale (MADRS)) that led to termination from the study than lamotrigine monotherapy did.
Generalized anxiety disorder (GAD) is a prevalent illness often associated with considerable discomfort and dysfunction. It often co-occurs with bipolar disorder. Traditional treatments of the primary syndrome (occurring in the absence of bipolar disorder) involve serotonin-selective antidepressants and serotonin-noradrenergic reuptake inhibitors such as venlafaxine (Effexor) or duloxitine (Cymbalta). While these are often useful and lead to considerable improvement, they often do not lead to full remission of somatic or accompanying symptoms of insomnia.
Alternative treatment possibilities include the anticonvulsant pregabalin (Lyrica), which has been found effective in four placebo-controlled studies in GAD. A poster presentation by Joshi et al. at the American Psychiatric Association meeting in San Francisco in May 2009 also reported that pregabalin was more effective in reducing sleep disturbance than venlafaxine. Pregabaline is FDA-approved for seizures and fibromyalgia, but not for GAD or pain syndromes. Another treatment possibility is quetiapine (Seroquel), where not only have there been positive efficacy in placebo-controlled studies of patients with GAD, but the patients also experienced improvement in sleep.