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Saturday, January 3, 2015

January 2014

FDA reporting mental health drug Ziprasidone (Geodon) associated with rare but potentially fatal skin reactions.

The U.S. Food and Drug Administration (FDA) is warning that the antipsychotic drug ziprasidone (marketed under the brand name, Geodon, and its generics) is associated with a rare but serious skin reaction that can progress to affect other parts of the body. A new warning has been added to the Geodon drug label to describe the serious condition known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Patients who have a fever with a rash and/or swollen lymph glands should seek urgent medical care. Health care professionals should immediately stop treatment with ziprasidone if DRESS is suspected.
Ziprasidone is an antipsychotic drug used to treat the serious mental health disorders schizophrenia and bipolar I disorder. Ziprasidone helps restore certain natural substances in the brain and can decrease hallucinations, delusions, other psychotic symptoms, and mania. To work properly, ziprasidone should be taken every day as prescribed. Patients should not stop taking their medicine or change their dose without first talking to their health care professional.

DRESS may start as a rash that can spread to all parts of the body. It can include fever, swollen lymph nodes, and inflammation of organs such as the liver, kidney, lungs, heart, or pancreas. DRESS also causes a higher-than-normal number of a particular type of white blood cell called eosinophils in the blood. DRESS can lead to death.

FDA reviewed information from six patients in whom the signs and symptoms of DRESS appeared between 11 and 30 days after ziprasidone treatment was started. None of these patients died (see Data Summary). Based on this information, FDA required the manufacturer of Geodon to add a new warning for DRESS to the Warnings and Precautions section of the drug labels for the capsule, oral suspension, and injection formulations.


Tests May Soon Predict Alzheimer’s. Do You Want to Know?

Before Alzheimer’s begins to steal the mind, hints of the disorder circulate in the blood, potentially giving people a way to find out if they’ll fall victim to the disease years in the future.

The question is: Would you want to know?

This year, research teams announced blood tests under development to diagnose Alzheimer’s before symptoms arise, including one that predicted the disease’s onset with 100 percent accuracy a decade in advance. While the tests will likely help drug companies evaluate medicines, they’ll also create wrenching personal and ethical dilemmas for patients who will have to live with the knowledge that they’re destined to develop the disease, the sixth-leading cause of death in the U.S., according to the Alzheimer’s Association.

For patients like Pamela Freeman’s mother, knowing Alzheimer’s was coming would have been a “tremendous help” to her family. Around age 75, her mother began to make unexplained, nonsensical purchases, stashing boxes all over the house. A relative talked her into a bad investment. “She never would have done this when she was in her right mind,” Freeman said. By the time the family realized she had Alzheimer’s and needed help, three years later, $10,000 was gone.

A predictive test might have changed that. “Had we known it was coming, there would have been a lot better outcome,” Freeman said. Before she died at age 87, her mother ran out of money, and Freeman and her siblings had to help cover her expenses.


Methamphetamine Use Triples Parkinson's Risk

Drug and Alcohol Dependence Journal


Despite widespread use of methamphetamine and other amphetamine-type stimulants (METH/AMPH), little is known about the long-term medical consequences of METH/AMPH abuse and dependence. Preclinical neurotoxicity findings raise public health concerns that these stimulants may damage dopamine neurons, resulting in dopamine-related disorders such as Parkinson's disease (PD).

A retrospective design was used to examine statewide medical records (1996 through 2011) linked to the Utah Population Database. Individuals 30 years or older on December 31, 2011 were assigned to a METH/AMPH cohort (ICD-9-CM 304.4, 305.7, 969.7, E854.2; N = 4935), a cocaine cohort (ICD-9-CM 304.2, 305.6, 968.5, E855.2; N = 1867) or a population cohort unexposed to drugs or alcohol for control selection. A competing-risks, proportional hazards model was used to determine whether the METH/AMPH or cocaine cohorts were at increased risk of developing PD (ICD-9-CM 332.0) or PD/parkinsonism/essential tremor (PD/PT; ICD-9-CM 332.0, 332.1, 333.0, 333.1) compared to individually sex- and age-matched controls (5:1 control to case ratio; N = 34,010).

In METH/AMPH users, we observed an increased risk of PD and PD/PT (HRPD = 2.8, 95%CI 1.6–4.8, P < 10−3; HRPD/PT = 3.1, 95%CI 1.9–4.9, P < 10−4) compared to population-based controls. Conversely, cocaine users exhibited no elevated risk of PD compared to controls.

We observed a near three-fold increased risk of PD in METH/AMPH users vs. controls which confirms prior observations and supports that PD risk in users may be higher than previous estimates. A suggestion that female and male users may differ in PD susceptibility warrants further study.


Twitter Posts May Shine a Fresh Light on Mental Illness Trends - Johns Hopkins University

Newswise — Johns Hopkins computers scientists, who have already used Twitter posts to track flu cases, say their techniques also show promise as a tool to gather important information about some common mental illnesses.
By reviewing tweets from users who publicly mentioned their diagnosis and by looking for language cues linked to certain disorders, the researchers say, they’ve been able to quickly and inexpensively collect new data on post-traumatic stress disorder, depression, bipolar disorder and seasonal affective disorder.
In research presented at three scientific conferences this year, the scholars described how their techniques of mining public data have yielded fresh numbers on cases of these illnesses, allowing for analyses that were previously difficult or expensive to obtain. The scholars emphasized, however, that their findings did not disclose the names of people who publicly tweeted about their disorders.
The researchers said their goal is to share with treatment providers and public health officials some timely additional information about the prevalence of certain mental illnesses. Using computer technology to sift through tweets, they said, can help address the slow pace and high costs associated with collecting mental heath data through surveys and other traditional methods.
“With many physical illnesses, including the flu, there are lots of quantifiable facts and figures that can be used to study things like how often and where the disease is occurring, which people are most vulnerable and what treatments are most successful,” said Glen Coppersmith, a Johns Hopkins senior research scientist who has played a key role in the project. “But it’s much tougher and more time-consuming to collect this kind of data about mental illnesses because the underlying causes are so complex and because there is a long-standing stigma that makes even talking about the subject all but taboo.”
Coppersmith, who is affiliated with the university’s Center for Language and Speech Processing and its Department of Applied Mathematics and Statistics, added, “We’re not aiming to replace the long-standing survey methods of tracking mental illness trends. We believe our new techniques could complement that process. We’re trying to show that analyzing tweets could uncover similar results, but could do so more quickly and at a much lower cost.”
Earlier this year, Coppersmith, with Johns Hopkins colleagues Mark Dredze and Craig Harman, presented two papers describing their methods at two professional conferences in Baltimore and Ann Arbor, Mich.
Also, in August, at the Joint Statistical Meetings in Boston, Coppersmith and colleagues from the U.S. Naval Surface Warfare Center spoke about their promising early results in an ongoing study that uses Twitter posts to study mental illness in particular geographic areas.
Their analyses indicated that PTSD was more prevalent at military installations that frequently deployed during the recent Iraq and Afghanistan conflicts, and that signs of depression were more evident in locations with higher unemployment rates. While neither of these findings is surprising, they demonstrate that analyzing Twitter posts could become a useful yardstick in quickly measuring mental health trends, particularly after dramatic events such as natural disasters and military conflicts.
The computer algorithms used to discover mental health data from tweets look for words and language patterns associated with these ailments, including word cues linked to anxiety and insomnia, and phrases such as “I just don’t want to get out of bed.” The formula for zeroing in on mental health cases was based on a review of more than 8 billion tweets. The technique is built upon earlier Johns Hopkins work led by Dredze that successfully used Twitter posts to track outbreaks of the flu.
“Using Twitter to get a fix on mental health cases could be very helpful to health practitioners and governmental officials who need to decide where counseling and other care is needed most,” said Dredze, an assistant research professor in the Whiting School of Engineering’s Department of Computer Science. “It could point to places where many veterans may be experiencing PTSD, for example, or to towns where people have been traumatized by a shooting spree or widespread tornado damage.”
The idea has begun to generate some positive attention. After a recent conference presentation on the team’s social media research, an editorial in the Boston Globe stated, “Twitter is, apparently, the quiet therapist to whom we reveal much more that we realize. As such, it could be a valuable public-health tool. More work needs to be done in considering how such information could be used while still preserving privacy, but it’s an inquiry worth pursuing.”
A recent Newsweek article on new high-tech methods of tracking mental health trends also quoted Coppersmith as saying, “Mental health is something that has touched every single one of us at some point in our lives, whether it’s a personal experience or watching family or friends go through it. I don’t know how you can’t attack this problem. This is the one everyone should care about.”
In November, the Johns Hopkins team hosted a 48-hour hack-a-thon, bringing together scholars from six universities and a handful of industry partners to foster collaboration and innovation on these topics. The hack-a-thon was organized to prepare for the second Computational Linguistics and Clinical Psychology workshop, which will be held in Denver next spring in conjunction with the 2015 Conference of the North American Chapter of the Association for Computational Linguistics. Coppersmith and Dredze will serve on the program and organization committee, headed by a previous Johns Hopkins post-doctoral researcher, Margaret Mitchell, now at Microsoft Research.


FDA Approved Namzaric™, a Fixed-Dose Combination of Memantine Extended-Release and Donepezil Hydrochloride for Alzheimer’s Disease.

Calif., Dec. 24, 2014 /PRNewswire/ -- Actavis plc (NYSE: ACT) and Adamas Pharmaceuticals Inc. (NASDAQ: ADMS) today announced that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA) for Namzaric, a fixed-dose combination (FDC) of memantine hydrochloride extended-release, a NMDA receptor antagonist, and donepezil hydrochloride, an acetylcholinesterase inhibitor. Namzaric was approved for the treatment of moderate to severe dementia of the Alzheimer's type in patients stabilized on memantine hydrochloride and donepezil hydrochloride.

"Namzaric combines, in one capsule, two complementary therapeutic agents which are often co-prescribed as approximately 70% of Namenda XR patients are also on AChEI therapy.  Both Namenda XR and donepezil have proven efficacy and safety, for the treatment of moderate to severe Alzheimer's disease. Additionally, data has shown that combination therapy with Namenda XR and an AChEI demonstrated greater improvement in cognition and global function verses an AChEI alone," said David Nicholson, Actavis Senior Vice President, Global Brands R&D. "Along with our partner Adamas, we are proud that this important therapy will provide a convenient and innovative treatment option for Alzheimer's patients and caregivers that reduces the number of capsules they are required to take each day for the treatment of this devastating disease."

"We are excited about the approval of Namzaric — the first fixed-dose combination of extended-release memantine and donepezil — and look forward to its launch by Actavis in 2015," said Gregory T. Went, Ph.D., Chairman and CEO of Adamas Pharmaceuticals, Inc.  "Namzaric is also the first FDA-approved FDC product to emerge from Adamas' platform for modifying the pharmacokinetic profiles of approved drugs, and we look forward to developing additional new treatments for individuals with serious neurological CNS disorders."

Namzaric, formerly known as MDX-8704, is a once-daily oral capsule for patients currently taking memantine (10 mg twice daily or 28 mg extended-release once-daily) and donepezil 10 mg. In addition, the capsules can be opened to allow the contents to be sprinkled on food to facilitate dosing for patients who may have difficulty swallowing.

"When determining therapies for my patients in the moderate to severe stages of Alzheimer's disease, I consider the therapy's effectiveness, safety profile and its ease of administration. The FDA's approval of Namzaric offers a new therapeutic option that provides patients a fixed-dose combination of two treatments often prescribed together, in one capsule," said Gustavo Alva, MD, Neuropsychiatrist and Medical Director at ATP Clinical Research in Costa Mesa, CA and volunteer faculty member at University of California, Irvine.

Namzaric will be available in two dosage strengths, 28/10 mg (memantine extended release/donepezil) and 14/10mg (memantine extended release/donepezil) for patients with severe renal impairment. Memantine ER is the active ingredient in the currently marketed NAMENDA XR®, which is indicated for the treatment of moderate to severe dementia of the Alzheimer's type. Donepezil is the active ingredient in ARICEPT®, which is indicated for the treatment of mild to severe dementia of the Alzheimer's type. Actavis and Adamas collaborated on the development of the fixed-dose combination and Actavis will have exclusive U.S. commercialization rights, while Adamas will retain exclusive commercialization rights outside of the U.S. Actavis expects to launch Namzaric in the U.S. in the second quarter of 2015.

About the Clinical Trials 
The efficacy and safety of the coadministration of memantine HCl extended release and acetylcholinesterase inhibitors (AChEIs), including donepezil HCl, was based on the results of a randomized, double-blind, placebo-controlled trial of 677 outpatients on a stable dose of AChEIs. The clinical study was not conducted with Namazaric; however, bioequivalence of Namazaric with coadministered memantine HCl extended release and donepezil HCl was demonstrated. Approximately 68% of the patients randomized to receive either memantine HCl extended release 28 mg or placebo were taking donepezil as the AchEI at Baseline and throughout the study. The results of this study, demonstrated statistically significant improvement in cognition and global function for patients treated with NAMENDA XR 28 mg plus an AChEI compared to placebo plus an AChEI.

The most commonly observed adverse reactions seen with memantine hydrochloride extended-release in patients with moderate to severe Alzheimer's disease, defined as those occurring at a frequency of at least 5% in the memantine hydrochloride extended-release group and at a higher frequency than placebo, were headache, diarrhea, and dizziness.


Vitamin D Linked to Seasonal Depression

Medical Hypotheses Journal 


Seasonal affective disorder (SAD) is a polyfactorial and polygenetic disorder that involves biological and psychological sub-mechanisms that differentially involve depression, seasonality, circadian rhythms, retinal sensitivity, iris pigmentation, sleep factors, and the neurotransmitters involved with these systems. Within the framework of the polyfactorial conceptualization of SAD, we review the possible contributions of vitamin D3 with respect to the aforementioned sub-mechanisms. We hypothesize that rather than functioning primarily as a proximal or direct sub-mechanism in the etiology of SAD, vitamin D likely functions in a more foundational and regulative role in potentiating the sub-mechanisms associated with the depressive and seasonality factors. There are several reasons for this position: 1. vitamin D levels fluctuate in the body seasonally, with a lag, in direct relation to seasonally-available sunlight; 2. lower vitamin D levels have been observed in depressed patients (as well as in patients with other psychiatric disorders) compared to controls; 3. vitamin D levels in the central nervous system affect the production of both serotonin and dopamine; and 4. vitamin D and vitamin D responsive elements are found throughout the midbrain regions and are especially concentrated in the hypothalamus, a region that encompasses the circadian timing systems and much of its neural circuitry. We also consider the variable of skin pigmentation as this may affect levels of vitamin D in the body. We hypothesize that people with darker skin pigmentation may experience greater risks for lower vitamin D levels that, especially following their migration to regions of higher latitude, could contribute to the emergence of SAD and other psychiatric and physical health problems.


Mortality Associated With Antipsychotic Dosage Reveals U-Shaped Curve - Schizophrenia Bulletin

Schizophrenia Bulletin


It is generally believed that long-term use of antipsychotics increases mortality and, especially, the risk of cardiovascular death. However, there are no solid data to substantiate this view.

We identified all individuals in Sweden with schizophrenia diagnoses before year 2006 (N = 21 492), aged 17–65 years, and persons with first-episode schizophrenia during the follow-up 2006–2010 (N = 1230). Patient information was prospectively collected through nationwide registers. Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010.

Compared with age- and gender-matched controls from the general population (N = 214920), the highest overall mortality was observed among patients with no antipsychotic exposure (hazard ratio [HR] = 6.3, 95% CI: 5.5–7.3), ie, 0.0 defined daily dose (DDD)/day, followed by high exposure (>1.5 DDD/day) group (HR = 5.7, 5.2–6.2), low exposure (<0.5 DDD/day) group (HR = 4.1, 3.6–4.6), and moderate exposure (0.5–1.5 DDD/day) group (HR = 4.0, 3.7–4.4). High exposure (HR = 8.5, 7.3–9.8) and no exposure (HR = 7.6, 5.8–9.9) were associated with higher cardiovascular mortality than either low exposure (HR = 4.7, 3.7–6.0) or moderate exposure (HR = 5.6, 4.8–6.6). The highest excess overall mortality was observed among first-episode patients with no antipsychotic use (HR = 9.9, 5.9–16.6).

Among patients with schizophrenia, the cumulative antipsychotic exposure displays a U-shaped curve for overall mortality, revealing the highest risk of death among those patients with no antipsychotic use. These results indicate that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than antipsychotic treatment when used in adequate dosages.


Small Study: Nitrous Oxide May Provide Swift Relief From Severe Depression.

Biological Psychiatry Journal


NMDA receptor antagonists, such as ketamine, have rapid antidepressant effects in patients with treatment-resistant depression (TRD). We hypothesized that nitrous oxide, an inhalational general anesthetic and NMDA receptor antagonist, may also be a rapidly acting treatment for TRD.

In this blinded, placebo-controlled crossover trial 20 TRD patients were randomized to a 1-hour inhalation of 50% nitrous oxide/50% oxygen or 50% nitrogen/50% oxygen (placebo control). Primary endpoint was the change on HDRS-21 24 hours after treatment.

Mean duration of nitrous oxide treatment was 55.6 ± 2.5 (SD) minutes at a median inspiratory concentration of 44% (37 – 45%, IQR). In two patients nitrous oxide treatment was briefly interrupted and in three discontinued. Depressive symptoms improved significantly at 2 hours and 24 hours after receiving nitrous oxide compared to placebo (mean HDRS-21difference at 2 hours: -4.8 points, 95% CI -1.8 to – 7.8 points, p= 0.002; at 24 hours: -5.5 points, 95% CI -2.5 to -8.5 points, p<0.001; comparison between nitrous oxide and placebo: p<0.001). Four patients (20%) had treatment response (reduction ≥50% on HDRS); three patients (15%) a full remission (HDRS ≤ 7 points) after nitrous oxide, compared to one patient (5%) and none after placebo (odds ratio [OR] for response 4.0, 95% CI 0.45 – 35.79; OR for remission 3.0, 95% CI 0.31 – 28.8). No serious adverse events occurred; all adverse events were brief and of mild to moderate severity.

This proof-of-concept trial demonstrated that nitrous oxide has rapid and marked antidepressant effects in patients with treatment-resistant depression.


Moderate coffee consumption may lower the risk of Alzheimer's disease by up to 20 percent

Drinking 3-5 cups of coffee per day may help to protect against Alzheimer's Disease, according to research highlighted in an Alzheimer Europe session report published by the Institute for Scientific Information on Coffee (ISIC), a not-for-profit organisation devoted to the study and disclosure of science related to coffee and health.

The number of people in Europe aged over 65 is predicted to rise from 15.4% of the population to 22.4% by 20251 and, with an aging population, neurodegenerative diseases such as Alzheimer's Disease are of increasing concern. Alzheimer's Disease affects one person in twenty over the age of 65, amounting to 26 million people world-wide

Recent scientific evidence has consistently linked regular, moderate coffee consumption with a possible reduced risk of developing Alzheimer's Disease. An overview of this research and key findings were presented during a satellite symposium at the 2014 Alzhemier Europe Annual Congress.

The session report from this symposium highlights the role nutrition can play in preserving cognitive function, especially during the preclinical phase of Alzhemier's, before symptoms of dementia occur. The report notes that a Mediterranean diet, consisting of fish, fresh fruit and vegetables, olive oil and red wine, has been associated with a reduced risk for development of Alzheimer's Disease. Research suggests that compounds called polyphenols are responsible for this protective effect, these compounds are also found in high quantities in coffee.

Epidemiological studies have found that regular, life-long moderate coffee consumption is associated with a reduced risk of developing Alzheimer's Disease with the body of evidence suggesting that coffee drinkers can reduce their risk of developing the disease by up to 20%. A recent paper, suggested that moderate coffee consumption was associated with a lower risk of developing dementia over a four year follow-up period, however the effect diminished over longer follow up period.

Finally, the report explores the compounds within coffee, which may be responsible for this protective effect, identifying caffeine and polyphenols as key candidates. Caffeine helps prevent the formation of amyloid plaques and neurofibrulary tangles in the brain - two hallmarks of Alzheimer's Disease. In addition to this, both caffeine and polyphenols reduce inflammation and decrease the deterioration of brain cells - especially in the hippocampus and cortex, areas of the brain involved in memory.

Dr. Arfram Ikram, an assistant professor in neuroepidemiology at Erasmus Medical Centre Rotterdam, presented his findings at the symposium. He commented: "The majority of human epidemiological studies suggest that regular coffee consumption over a lifetime is associated with a reduced risk of developing Alzheimer's Disease, with an optimum protective effect occurring with three to five cups of coffee per day."

Dr. Iva Holmerova, vice chairperson of Alzheimer Europe, commented: "The findings presented in this report are very encouraging and help to develop our understanding of the role nutrition can play in protecting against Alzheimer's Disease. Coffee is a very popular beverage enjoyed by millions of people around the world and I'm pleased to know that moderate, lifelong consumption can have a beneficial effect on the development of Alzheimer's Disease."

The session report details the key scientific research presented by Dr. Neville Vassallo, Dr. Arfan Ikram and Dr. Astrid Nehlig during a session entitled: Nutrition and Cognitive Function, which took place on the 23rd October in Glasgow, UK.


US FDA approves the labeling update of Abilify Maintena (aripiprazole) for extended-release injectable suspension to describe new clinical data for the treatment of acutely relapsed adults with schizophrenia

H. Lundbeck A/S (Lundbeck) and Otsuka Pharmaceutical Co., Ltd. (Otsuka) announced that the US Food and Drug Administration (FDA) approved the labeling update of Abilify Maintena® (aripiprazole) for extended-release injectable suspension. The approval was based on results from a controlled clinical study of acutely relapsed adults with schizophrenia. Efficacy was demonstrated in a 12-week randomized, double-blind placebo-controlled study, which showed treatment with Abilify Maintena (with concomitant oral aripiprazole for the first two weeks) significantly improved symptoms with an acceptable safety and tolerability profile in adult patients experiencing an acute relapse of schizophrenia with an acceptable safety and tolerability profile.These data were published in the November print edition of The Journal of Clinical Psychiatry.

Abilify Maintena, an atypical antipsychotic, was first approved by the FDA in February 2013 for intra-muscular (gluteal) use for the treatment of schizophrenia. Efficacy was demonstrated in a placebo-controlled, randomized withdrawal maintenance trial in adult patients with schizophrenia, and additional support for efficacy was derived from oral aripiprazole trials.

"An acute exacerbation of psychotic symptoms, also referred to as disease relapse, is a key consideration in the management of schizophrenia, and can occur when a patient no longer responds to or stops taking antipsychotic medication," said study investigator John M. Kane, M.D., Chairman of Psychiatry, The Zucker Hillside Hospital, and Vice President, Behavioral Health Services, North Shore-LIJ Health System. "These data — and the updated product labeling — confirm the utility of Abilify Maintena in acutely relapsed adult patients, giving physicians an option to consider for both the initial and ongoing treatment of patients with schizophrenia."

Clinical trials results

Efficacy of Abilify Maintena (aripiprazole) for the treatment of acutely relapsed adults with schizophrenia was demonstrated in a 12-week multicenter, randomized, double-blind, placebo-controlled trial. The primary measure used for assessing psychiatric signs and symptoms was the Positive and Negative Syndrome Scale (PANSS), a 30-item scale that measures positive and negative symptoms of schizophrenia and general psychopathology, using a rating scale of 1 (absent) to 7 (extreme); the primary endpoint was pre-specified to be measured as the change from baseline to week 10 of treatment. All patients entering the trial were inpatients who met DSM-IV-TR criteria for schizophrenia and experienced an acute psychotic episode as defined by both PANSS total score of 80 or higher, and a PANSS score greater than 4 on each of four specific psychotic symptoms (conceptual disorganization, hallucinatory behavior, suspiciousness/persecution, unusual thought content). Patients had a mean PANSS total score of 103 at study entry.i

A total of 339 patients received double-blind treatment with Abilify Maintena 400 mg (n=167) or placebo (n=172), with 64.3% (Abilify Maintena) and 49.4% (placebo) of patients completing 10 weeks of treatment. The primary efficacy outcome was change from baseline to 10-week endpoint in PANSS total score and demonstrated greater improvement with Abilify Maintena than with placebo (-26.8 vs. -11.7, respectively, p<0.0001); statistically significant improvements with Abilify Maintena were shown at all time points measured from week 1-12.i The key secondary efficacy outcome was change from baseline to 10-week endpoint in Clinical Global Impression Severity of Illness Scale (CGI-S) score and also showed statistically greater improvement with Abilify Maintena than with placebo (-1.4 vs. -0.6, respectively, p<0.0001).


Online Journals:

Journal of Clinical Psychopharmacology - February 2015 - Volume 35, Issue 1

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