Patient Counseling Increases Reported Side Effects in Patients with Schizophrenia

One of the number one ways that pharmacist can help patients is by counseling them on their medications.  Side effects of a medication is something that almost every patient is concerned about before taking a new medication.  Antipsychotics, treatment for Schizophrenia, have a large side effect profile.  Sedation, sexual dysfunction, and extrapyramidal symptoms are some of the side effects patients can experience from these medications.  This studies aim was to see whether or not the number of patients that reported side effects from their antipsychotic medication increase after being counseled by a healthcare provider.  Nonadherence is a big problem that often leads to hospitalization of a patient.  Nonadherence is often caused by patients experiencing a side effect but they are not counseled as to whether or not they were supposed to expect that side effect.  This leads to the patient discontinuing the medication without properly talking to a provider.

The study was conducted by taking a survey to assess whether or not a patient was experiencing side effect symptoms from their antipsychotic medication.  The patient had to report whether or not they experienced side effects from their medication.  The study was conducted at two inpatient settings in Japan which ae the Sawa Hospital and the Hokuto Clinic Hospital.  The study was conducted with 87 patients.  Before the patients were counseled on their medications, 24 of the 87 patients reported experiencing side effects compared to the 60 patients that had reported that they experienced side effects after the counseling session.  These numbers show that patients do not always know that they are experiencing side effects from their medication.  It is important to counsel patients before they pick up their medication so that they know what to expect.  It is also important to be available to patients all the time so that they can have their unanswered questions answered.  Creating a comfortable trusting environment is also important when it comes to accurate retrieval of information.  This study shows the importance pharmacist have on patients therapy outcomes.

http://Australas Psychiatry. 2016 Feb 24. pii: 1039856216634825.

Persistence of metabolic monitoring for psychiatry inpatients treated with second-generation antipsychotics utilizing a computer-based intervention

This article goes over a novel technique to try and improve the quality of patient metabolic monitoring during the use of 2nd generation antipsychotics by using a computer interface and pop-up alert system. Patients taking 2nd generation psychotics can have side effects related to essential metabolic processes. These effects can include weight gain, diabetes occurrence, and others. Therefore the efficiency and rate at which metabolic parameters are important to prevention of further health problems. The metabolic parameters being measured were blood glucose levels, hemoglobin A1C, and a lipid panel, which were then compared to to the initial implementation.

The goal of the study was to determine if the computer system with pop-up alerts was a better option than conventional methods by measuring the rate of monitoring in an inpatient setting. A total of 129 patients (159 in the initial cohort) were monitored and the study was carried out over a period of 4 years. A comparison was done between the computerized physician order entry (CPOE) pop-up alert system and the conventional systems via long term chart reviews. Patient chart reviews were also used to determine if monitoring improved patient outcomes or alerted medical personnel to health risks.

The end result of the study is that the new computer pop-up alert system to did not significantly change monitoring rates. Although there were interventions from the psychiatry team as a result of the computerized system, which shows potential for the use of the system in the future.

We are learning about 2nd generation antipsychotics currently in POP.

How do you think techonology could be better implemented in this special patient population to improve outcomes?

Find this article here:

Lee J, Dalack GW, Casher MI, et al. Persistence of metabolic monitoring for psychiatry inpatients treated with second generation antipsychotics utilizing a computer-based intervention.            J Clin Pharm Ther. 2016 Feb 26. doi: 10.1111/jcpt.12368.

Xanomeline as a Possible Novel Treatment for Schizophrenia

In this study completed by Shekhar and fellow colleagues, xanomeline was tested for its efficacy in patients with schizophrenia. Xanomeline is a selective muscarinic receptor antagonist that currently has no FDA approved uses, but does have a non-FDA use for Alzheimer’s Disease. The trial design was a double-blind, placebo-controlled study that included 20 participants over the course of 12 weeks. The participants were screened using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression (CGI) scale. If they met the criteria for these two scales they were able to enter into the study.

For the first week of the study, patients were given 3 doses of placebo each day. If they continued to meet the criteria on the two tests by the end of the week, they were eligible to continue into the next stage. At this point, the 20 participants were split into even groups that would either receive 25 mg of xanomeline 3 times a day or placebo 3 times a day. After two days of this, the safety was evaluated and the dose was raised to 50 mg of xanomeline 3 times a day or 2 placebo tablets 3 times a day.

At the end of the 12 weeks, the participants were tested using the Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS). It was found that the xanomeline group did significantly better on these two tests than the placebo groups and also showed improvements in verbal learning and memory capability.

Do you think studies such as these show promise without comparison to a drug that is already approved by the FDA for Schizophrenia?

Shekhar A, Potter W, Lightfoot J, et al. Selective Muscarinic Receptor Agonist Xanomeline as a Novel Treatment Approach for Schizophrenia. Am J Psychiatry 2008; 165:1033–1039.

Detection of Circulating miRNA Levels in Schizophrenia

Schizophrenia is a mental disorder that can effect a person’s entire life: how they think, feel, and behave. Like other mental disorders its symptoms can be disabling. The disorder most commonly begins to show symptoms between the ages of 16 and 30 and the symptoms are divided into three categories: positive (psychotic behaviors), negative (disruption to normal emotions), and cognitive (changes in memory and thinking). It has been long known that genetics is a risk factor for development of the disorder, with multiple genes increasing the risk. A singular gene has not been found to cause the disorder itself, and diagnosis is currently only based upon symptoms. This past November, Wei and colleagues investigated whether the presence and concentration of circulating miRNA can become a diagnostic biomarker for Schizophrenia. miRNA are noncoding short RNA sequences that regulate gene expression and a variety of other cellular functions.

Two cohort studies were used in determining results. The first included 164 patients with schizophrenia and 187 control subjects. The plasma miRNA for each patient was profiled using three different genetic based technologies (Solexa sequencing, TaqMan Low-Density Array, and qRT-RCR). It was studied based on the expression signals.

The qRT-PCRs in the first were then compared with qRT-PCRs in the second which included 400 patients diagnosed with Schizophrenia, 213 control patients, and 162 patients with a nonschizophrenia psychiatric disorder.

Both studies revealed 8 miRNAs that were up-regulated in the patients with Schizophrenia. There were even two miRNAs that were upregulated in Schizophrenia but not in nonschizophrenia disorders. The two miRNAs were miR-130b and miR-193a-3p. Finding that these are upregulated, there is a potential for the development of a diagnostic biomarker, and even a drug therapy target.

Mental disorders are very hard to diagnosis and the possibility of a potential biomarker for a disorder that has previously only been able to be diagnosed by symptoms is very promising for those that may be affected by it. The knowledge of this is also a potential for drug target treatment and maybe even prophylaxis. Personally knowing someone who suffers from Schizophrenia, this really hit home and gave my a little hope for the future of those who are already affect and those who may be in the future.

Am J Psychiatry. 2015;172(11):1141-1147.

Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia

Vitamin B12 is crucial for brain development and function. This is because vitamin B12’s active metabolites are important cofactors for two reactions. One reaction involves the metabolite methylcobalamin (MeCbl), and it is folate dependent methylation of HCY to methionine by methionine synthase in the cytoplasm. The other metabolite, adenosylcobalamin (AdoCbl), is used as a cofactor for the conversion of methylmalonylCoA to succinylCoA by methylmalonyl CoA mutase in mitochondria. Despite us knowing this, vitamin B12’s role in the brain across the lifespan has not been investigated until this study.

In this study, the levels of five vitamin B12 species in postmortem human frontal cortexes of 43 control subjects were measured. These cortexes ranged from those of 19 week old fetuses to those of 80 year old individuals. Of the subjects, twelve of them were autistic and nine of them were schizophrenic.

The results of this study showed that total B12 levels were significantly lower in the front cortexes of the older control subjects 60 years and older. This reflected over a ten fold age dependent decline in the B12 metabolite MeCbl. Levels of another B12 metabolite, cyanocobalamin (CNCbl) were much higher in fetal brain samples, further showing that vitamin B12 levels decrease with age. The levels of MeCbl and AdoCbl in autistic and schizophrenic subjects were more than three fold lower than the controls that were the same age as these subjects, but who did not have autism or schizophrenia.

This study is interesting to me because it makes me wonder whether taking vitamin B12 supplements would help with aging, or improve the mental state of those with autism or schizophrenia. I feel that it may be beneficial for pharmacists to recommend these supplements to patients with autism or schizophrenia. However, it is important that if they do begin doing this that they counsel these patients or their caregivers on the common side effects of taking vitamin B12 supplements. Some of these side effects include joint pain, dizziness, headache, and nasopharyngitis.

PLoS ONE. 2016;11(1): 1-19.

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia

For schizophrenia that is treatment resistant, clozapine is the standard drug therapy. The high use of clozapine for this condition is largely based on one study conducted by Kane and colleagues that demonstrated its effectiveness. However, since then many clinical trials have been conducted for other second generation antipsychotics. In addition to this fact, clozapine is also noted to have many side effects. Thus, the researchers of this study found it necessary to conduct a meta-analysis to evaluate if clozapine is still the most effective treatment available for treatment-resistant schizophrenia. In order to conduct the meta-analysis, the researchers studied 40 single and double blind randomized clinical trials of adults with treatment-resistant schizoaffective disorder, schizophreniform disorder, or schizophrenia. The drugs involved in the studies were clozapine, haloperidol, olanzapine, and risperidone.

The results of the pairwise meta-analysis showed that olanzapine, clozapine and risperidone were significantly effective as therapies for treatment-resistant schizophrenia. Clozapine, however, was not the most effective of all the drugs. The data showed some inconsistencies due to sampling bias found in the trials. In addition, many of the clinical trials that the researchers would have liked to include in the study were unblinded and thus excluded. Therefore, it can be concluded that evidence for which antipsychotic medication is best for patients with treatment-resistant schizophrenia is limited. More research needs to be conducted to compare clozapine with second generation antipsychotics.

I found this article to be interesting because the researchers conducting this study took it upon themselves to question standard practices. I think it is important to continue studying treatments that are considered “standard” because it allows for continuous improvement in prescribing. If we never questioned ourselves, therapies would never be improved. In this case, clozapine had been shown to be more effective than first generation antipsychotics. However, its effectiveness was not proven over second generation antipsychotics. With the emergence of these newer drugs, I think it is important to reevaluate the situation and compare therapies. With this in mind, as future pharmacists we should try to always stay up to date on such research so that we are able to advise prescribers and patients on the most effective drug available for the indication being treated.

Samara M, Dold M, Gianatsi M, et al. Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia. Jama Psychiatry. 2016; published ahead of print.

Readmission Patterns and Effectiveness of Transitional Care Among Medicaid Patients With Schizophrenia and Medical Comorbidity

Transitional care refers to the process of continuing health care treatment between the time in which the patient is moved from one healthcare setting to another.  Recent studies have shown that implementation of transitional care practices can aid in the reduction or readmission rates for patients with a chronic disease state; however, there has not been information analyzing the utilization of transitional care in patients with a mental illness. For this reason, researchers from North Carolina aimed to look deeper into the effects that transitional care can have by focusing on a population of Medicaid patients who had both a mental illness and a chronic disease state.

In this study, researchers analyzed the effects that transitional care had on the population by monitoring hospital discharges and readmissions over the course of a year.  A total of 1,717 Medicaid patients met the criteria for the study and of this number 1,104 patients were provided with a transitional care assessment or intervention. The data collected from the study showed that patients receiving transitional care after a hospitalization for a non-psyciatric reason were much less likely to be readmitted 30 days after discharge (18% compared 27%).  This gap between the readmission rates of the two groups continued to have a level of significance throughout the year.  The same results were found to be true regarding patients who had initially been admitted to the hospital for a psychiatric reason.

I believe this study is important to understanding the role that healthcare professionals can have in affecting the health of a patient. The time that we give to provide personalized education to patients experiencing multiple chronic conditions can have a huge effect on the patients future health. This is something that is also beneficial to our nation’s healthcare system which experiences heavy costs in relation to improper management of a patient’s health after the time of discharge.  I would like to know more about how transitional care is currently being utilized in the  inpatient and outpatient setting so that I can further improve my patient care skills.


Metformin Treatment of Antipsychotic-Induced Dyslipidemia: An Analysis of Two Randomized, Placebo-Controlled Trials

Schizophrenic patients on antipsychotic medications tend to experience the adverse effect of dyslipidemia. At this time, no effective treatments have been established to treat this adverse effect. As a result, data was pooled from two randomized, placebo-controlled trials.  201 schizophrenic patients that experience antipsychotic-induced dyslipidemia were either given 1000 mg of metformin to take each day for 24 weeks, or a placebo.

After the 24 week period, the mean difference in the LDL values between individuals receiving metformin and those receiving the placebo treatment decreased by 1.02 mmol/L. Only 25.3% of patient in the metformin group had LDL levels greater than or equal to 3.37 mmol/L, while 64.8% of those in the placebo group had LDL levels greater than or equal to that. It is evident that metformin is effective in reversing antipsychotic-induced dyslipidemia. This study also showed that metformin helped people on antipsychotics lose weight, lowered their total cholesterol and triglyceride levels, and increased their HDL levels. Additionally, insulin resistance can be induced by antipsychotics, and metformin would help with this as well.

After reading about this study, I am wondering whether automatically putting schizophrenic patients on metformin as well as antipsychotics should become the normal protocol. Should this happen, or should we as pharmacists monitor their cholesterol and insulin levels while they are on antipsychotics and only suggest they begin metformin if they exhibit any of the aforementioned adverse effects? If we do put these patients on metformin,  how should we counsel and monitor them?

Mol. Psychiatry. 2016 Jan 26;doi:10.1038/mp.2015.221.





Quetiapine safety in older adults: a systematic literature review

Quetiapine (Seroquel) is a second-generation antipsychotic that is used for many indications including schizophrenia and bipolar disorder. Off label indications include behavioral and psychological symptoms of dementia (BPSD). There are no systematic reviews on quetiapine in older adults, and the goal of this literature review was to review the safety profile and study adverse effects in this vulnerable population.

A systematic literature review was done using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases that were searched were CINAHL, PubMed, Medline, PsycInfo and Cochrane Library.

The most commonly found adverse effects were somnolence (25-39%), dizziness, headache, postural hypotension, and weight gain. Quetiapine was found to have significantly more cognitive impairment when compared to placebo, as well as higher rates of falls and increased mortality in patients with Parkinson’s disease. Controversially, it was found that quetiapine did not have any adverse effects in patients with dementia. Quetiapine was then compared to risperidone (quetiapine is metabolized to the active metabolite of risperidone so they are very similar drugs however they are metabolized differently in the body) and it was found that quetiapine had an increased rate for falls and injury, however less risk for mortality and reduced cardiovascular events compared to risperidone.

These findings show that consideration should be given to prescribing quetiapine in older adults. The percentage of somnolence and falls/injuries reported are very large and this is a huge concern for the older population. Pharmacists and doctors must anticipate and weigh these adverse effects against the therapeutic benefits when putting an older patient on quetiapine.

El-Saifi, N., Moyle, W., Jones, C. and Tuffaha, H. (2016), Quetiapine safety in older adults: a systematic literature review. Journal of Clinical Pharmacy and Therapeutics, 41: 7–18. doi: 10.1111/jcpt.12357

Pharmacogenomics & A New Target Therapy for Schizophrenia

Schizophrenia is one of the earliest recorded and least understood mental illness that we face today. Schizophrenia is a chronic and severe mental disorder characterized by hallucinations, delusions, movement disorders, and withdrawal from others. The current treatments for schizophrenia are limited, and they tend to treat only the psychotic symptoms of the disease. Targeting the cause of the disease has been – until now – impossible, as much remains unknown about the pathology of schizophrenia. While it has been known that schizophrenic symptoms are associated with excessive synaptic pruning (removal of synapses in the brain during adolescence and young adulthood) – and this correlates to the typical interval of onset of the disease during adolescence and young adulthood – the exact mechanism of how the disease develops has remained a mystery until now.

A collaborative research team from Broad Institute, Harvard Medical School, and Boston Children’s Hospital has recently published results that suggest a genetic basis for the onset of schizophrenia symptoms. Their genetic analysis of almost 65 000 people points to overexpression of the complement component 4 (C4) gene in the expression of Alzheimer’s disease. Complement protein genes can be present in varying alleles, and different alleles (DNA) directly affect the overall expression level (mRNA) of the gene. In other words, the variation of the genetic sequence of the gene directly impacts the amount of protein produced.

Complement proteins have a well-established role in the immune system, where they tag foreign pathogens for destruction by phagocytic immune cells. However, their role in neurology is an entirely novel discovery. Researchers were able to localize the C4 proteins to neural synapses in humans, and proved that in mice they contributed to the synaptic pruning process during postnatal development.

Because of this study, a molecular basis of schizophrenia as a disease is now in the works. By understanding the molecular cause of the disease, researchers will be better able to identify therapeutic targets and develop new pharmaceutics and other treatments which go after the cause and onset of disease, rather than just managing the symptoms.

This article made me think about the emerging role of genetics in healthcare. By understanding the genetic expression associated with schizophrenia, researchers will be better able to pinpoint the molecular basis of the disease and create better therapeutics which target the cause of the disease, instead of just the symptoms. There is a new intersection of basic science (genetics) and therapeutics (pharmacy and medicine) that is entirely new to science and healthcare. This makes me wonder – should we be focusing more on basic science, such as genetics, during our professional curriculum so that we will be able to both understand and contribute to emerging healthcare technologies, such as pharmacogenetics? Or is that role reserved for PhDs?

Additionally, what other types of disease states are there out there for which pharmacogenetic analysis would help us to determine the cause, and can we create better medicines that target the cause rather than just the symptoms? One that I think of are benzodiazepines, which treat only the physical symptoms of anxiety instead of the psycho-cognitive causes.

Sekar A, Bialas AR, de Rivera H, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530;177–183.