Randomized Trial Assessing the Effectiveness of a Pharmacist-Delivered Program for Smoking Cessation

Considering how accessible pharmacists are and how well suited they are to interact with patients obtaining smoking cessation medications, pharmacists can be instrumental in delivering programs to patients and hopefully improve quit rates for smokers. This study explored the idea of utilizing a pharmacist team (a licensed clinical pharmacist and APPE students) in order to deliver a smoking cessation program face-to-face. The researchers compared outcomes from this approach with that of a method that involved brief telephone assistance to patients aiming to quit smoking. Outcomes were measured through the 7-day point prevalence quit rates, Fagerstrom Test for Nicotine Dependence scale, Perceived Stress Scale, and Center for Epidemiological Studies Short Depression Scale, as well as questionnaires regarding self-efficacy, motivation to quit smoking, and withdrawal symptoms. Biological measures of smoking, including cotinine levels, were also assessed. In addition to the two interventions, participants had a choice to receive either bupropion IR (Zyban®) tablets or nicotine patches.

The group receiving face-to-face treatment from the pharmacist team had a quit rate of 28% confirmed by the 7-day point prevalence and cotinine levels, while the standard care group receiving phone calls had a quit rate of 11.8%. Pharmacist-delivered face-to-face care seems to be beneficial in improving outcomes for those wanting to quit smoking. Perhaps collaborative practice agreements that allow pharmacists to prescribe smoking cessation medications can be developed to help improve quit rates. Pharmacists can be uniquely suited to this approach as they are so accessible and can help patients through all the aspects of taking smoking cessation medications– dispensing, counseling, and monitoring for efficacy, safety, and adherence.


Dent LA, Harris KJ, Noonan CW. Randomized trial assessing the effectiveness of a pharmacist-delivered program for smoking cessation. Ann Pharmacother. 2009; 43:193-201.

Sleep is More Sensitive to High Doses of Caffeine in the Middle Years of Life

Many of us may be aware that caffeine can keep you up late into the night, but the power of caffeine to affect sleep may actually be stronger in middle-aged adults. This study examined the administration of high (400 mg) and low (200 mg) doses of caffeine and aspects of sleep in young (20-30 years old) and older (40-60 years old) adults. A double-blind cross-over design was used with stratified randomization including 22 participants in each category (young and old). Electroencephalographic electrodes measured sleep latency (essentially the time it takes to fall asleep), total sleep duration, time spent in each sleep stage, and sleep efficiency.

In general, the older adult group was more sensitive to the effects of the higher dose of caffeine compared to the younger group. The effects of the lower dose did not differ significantly between the age groups. Specifically, given the higher dose, the older group took more than twice as long to fall asleep, experienced shorter total sleep times (by about 1.5 hours), and experienced reduced sleep efficiency as well as reduced amounts of short wave sleep and rapid eye movement sleep. The younger group actually experienced enhanced stage 1 sleep when given the 400 mg dose. Despite the age groups having similar salivary caffeine concentrations across sampling times, they experienced different effects. This can be due to age-related changes in the adenosinergic system– such as reduced A1 binding of adenosine and increased binding of A2a receptors and increased adenosine-forming enzymes– that result in a complex interaction between age and dosing of caffeine. Caffeine expresses its wakeful effects via adenosine antagonism.

People aged 50-60 years old consume the most caffeine on average amongst the adult population. This same subset of adults also experiences vast changes in sleep independent of caffeine consumption. With these facts and the results of this study in mind, it seems that this population is vulnerable to poorer sleep. Also considering how important sleep is to overall health and well-being, it seems that middle-aged adults should exercise caution in consuming caffeine. For reference, four cups of coffee may have about the same amount of caffeine as the high dose group (assuming about 95 mg caffeine per cup of coffee). From my limited experience with patients at SilverScripts, I have already seen that some older patients consume that much caffeine on a daily basis. As student pharmacists, we can inform our patients that consuming a lot of caffeine may lead to negative effects, including sleep disturbances as well as others not discussed in this study.


Robillard R, Bouchard M, Cartier A, et al. Sleep is more sensitive to high doses of caffeine in the middle years of life. J Psychopharmacol. 2015; 29(6):688-97

Simvastatin as an Adjuvant Therapy to Fluoxetine in Patients with Moderate to Severe Major Depression

Statins may not just be for dyslipidemia– this study provides evidence that they can be used as an adjuvant therapy with antidepressants. Statins and major depressive disorder (MDD) are not as unrelated as they may seem. Many processes mitigated by statins, like inflammation, oxidative stress, and vascular abnormalities, are involved in major depressive disorder. Statins have also been found to have effects on other neurological disorders, such as Alzheimer’s Disease and Multiple Sclerosis. Animal studies have shown that statins inhibit NMDA, which could potentially be therapeutic for those with depression.

This study examined the effects of simvastatin therapy (20 mg daily and later 40 mg daily) along with fluoxetine for those with MDD. Adherence, Hamilton Depression Rating Scale, and adverse events were assessed. Those in the simvastatin/fluoxetine group had significantly improved depressive symptoms than the placebo group receiving fluoxetine alone, and they even showed significant improvement early in the trial. It should be noted, however, that this study was short (6 weeks) and small in sample size.

Previous studies showed mixed/ inconclusive evidence for the efficacy of statins in improving depressive symptoms, but this study added to the evidence supporting adjuvant therapy with statins for MDD. Any step in the direction of improving symptoms for those with depressive is a positive step as current antidepressants are not effective in about 30% of patients. The mechanism of how statins can affect depression is not completely understood, but it likely involves NMDA receptors, glutamate uptake, and protecting neurons from glutamate-induced cell death. Some of these statin effects may be independent of the HMG-CoA enzyme inhibition action of the medication.

Does this seem like a promising approach to treating depression? How would patients react to taking an extra medication and possibly enduring some adverse effects, such as muscle pain, for a small improvement in depressive symptoms?

Gougol A, Zareh-Mohammadi N, Raheb S, et al. Simvastatin as an adjuvant therapy to fluoxetine in patients with moderate to severe major depression: A double-blind placebo-controlled trial. Psychopharmacol. 2015; 29:575-81.

Pilot study of Psilocybin in the Treatment of Tobacco Addiction

It seems strange that a drug of abuse, psilocybin, could be used to treat dependence of another drug, nicotine– but this study explores the potential efficacy of this unconventional therapy. Previous research from the 1950s-1970s showed that hallucinogens may be effective in treating drug dependence, such as alcoholism and opioid dependence. A more recent study, performed with the rigor and controls of modern research, has shown the potential for psilocybin to reduce anxiety and depression in those with advanced stage cancer and that these effects lasted well beyond the time of administration. Typical smoking cessation pharmacotherapy result in modest 6-month success rates (often less than 35%), so this study aimed to test the safety and potential efficacy of using psilocybin for smoking cessation.

This study recruited 15 subjects to participate in a 15-week open label pilot trial. Inclusion criteria was smoking at least 10 cigarettes a day, having several unsuccessful past attempts at quitting, and current desire to quite. Every participant went to a weekly cognitive behavioral therapy session for the first 4 weeks and then received a moderate dose (20 mg/ 70 kg) of psilocybin at week 5. Participants also set a target quit date (TQD) for the day they were receiving their first dose of psilocybin. Two additional psilocybin administrations were offered at weeks 7 and 13 with optional higher dosing (30 mg/ 70 kg). These administrations were intended to be additional quit opportunities for those who did not remain abstinent after the first administration. Participants met with staff to reflect each week throughout the study as well as after each psilocybin session. They also received quick phone calls from the staff for 2 weeks after the TQD for encouragement to quit.

Many measures were taken to ensure safety. Blood pressure and heart rate were monitored throughout the psilocybin sessions, and a physician and rescue medications were available in case adverse events occurred. At each session, participants were encouraged to lie on a couch, wear an eye mask, and listen to a music program. The staff provided interpersonal support to manage any effects of the drug. There were no clinically significant adverse effects experienced by any of the participants during any of the sessions, although blood pressure and heart rate were slightly elevated.

Outcomes measured in this study included exhaled carbon monoxide and urinary cotinine levels, both of which are biological indicators of smoking. Psychological aspects of smoking and dependence were measured through various tests and questionnaires, including the smoking timeline follow-back assessment, Fagerström Test for Cigarette Dependence, Questionnaire on Smoking Urges, Smoking Abstinence Self-Efficacy scale, and Wisconsin Smoking Withdrawal Scale. The effects of psilocybin were monitored through other questionnaires including the Visual Effects Questionnaire, a post-session headache interview, Mysticism Scale, States of Consciousness Questionnaire, Persisting Effects Questionnaire, and a questionnaire to measure if patients believed psilocybin had been efficacious in aiding smoking cessation.

12 out 15 (80%) of the participants demonstrated abstinence at the 6 month follow up via questionnaires and carbon monoxide/ cotinine levels (although 3 of the participants reported self-corrected lapses). There were signifiant reductions in self-reported daily smoking, carbon monoxide and cotinine levels, as well as significant differences in Smoking Abstinence Self-Efficacy confidence, Smoking Abstinence Self-Efficacy temptation, Questionnaire on Smoking Urges, and Wisconsin Smoking Withdrawal Scale scores. Reasons people claimed psilocybin helped with quitting included changing their outlook toward the future, strengthening their confidence in quitting, and changing life priorities and values. Only 1 participant reported that psilocybin did not aid smoking cessation. Participants who managed to quit were able to quit after only the first administration.

More studies, particularly controlled studies, would have to be conducted to support the efficacy of psilocybin in smoking cessation, but this study did show that it can be safe and feasible as an adjunct to smoking cessation treatment. This is promising when considering that current therapies involve many adverse effects and have lower quit rates. It is interesting that only one or a few doses needed to be administered in order for psilocybin to have a lasting effect on smoking cessation. It is also interesting to consider what the mechanism may be as it is not clear from this study how psilocybin can potentially affect smoking habits. While psilocybin is a Schedule I drug, there is no clear evidence that it engenders addiction and this study administered it in a safe and controlled manner.

Johnson MW, et al. Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction. J Psychopharmacol. 2014; 28(11):983-92

Pain Affects Clinical Patterns and Treatment Outcomes for Patients With Major Depressive Disorder Taking Fluoxetine

Although pain is not listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM) as a symptom of major depressive disorder (MDD), previous studies have shown that a large proportion of patients with depressive report symptoms of pain. In addition, research has shown that pain and depression may share common pathways in the body. They may be connected through stress and the hypothalamic-pituitary-adrenal axis.

This study aimed to see how baseline levels of pain affect outcomes in patients treated for MDD with fluoxetine. Specifically, the study hypothesized that severity of baseline would be associated with poorer outcomes and a distinct clinical profile. For 6 weeks in an in-patient hospital, 119 MDD patients were given 20 mg fluoxetine daily doses and monitored for various outcomes. Outcomes included adherence, pain severity and pain interference (measured by the body pain index of the Medical Outcomes Study Short-Form), symptom severity (measured by the Hamilton Rating Scale for Depression), social functioning (measured by the Work and Social Adjustment Scale), and adverse event severity (Utvalg for Kliniske Undersogelser Side Effect Rating Scale).

Results from this study showed that pain and multiple aspects of MDD were associated and that patients with higher baseline levels of pain experienced more severe depressive symptoms. Specifically, subjects with higher levels of pain had greater risk of suicide and stressful life events. They also had less improvement in depressive symptoms despite receiving the same fluoxetine treatment as well as more functional impairment.

This study reminds me of the pain lecture from Dr. Pruskowski as she also explained the connection between depression and pain. Being cognizant of this connection can help us better understand our patients as pharmacists. Perhaps we can inquire about MDD patients’ pain levels during medication therapy management. I would be curious to see if there is evidence supporting the use of pain treatments to help improve depressive symptoms in those with both severe pain and depression. If so, many patients may have a drug therapy problem of needing additional therapy.

Lin H, Wang F, Lin C. Pain affects clinical patterns and treatment outcomes for patients with major depressive disorder taking fluoxetine. J Clin Psychopharmacol. 2015; 35(6):661-6

Polymorphism Associated with the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depression

Are pharmacogenetics-based strategies the key to effective depression treatment? This study set out to dig deeper into this questions by researching additional polymorphisms affecting the efficacy of SSRIs. Previously, a polymorphism in the serotonin transporter linked promoter region was found to be associated with a difference in SSRI efficacy. This polymorphism, however, only explained a small amount of the differences in efficacy seen in the treatment of those with depression. So this study intended to find additional polymorphisms in the gene coding for the serotonin transporter (SLC6A4) accounting for different responses in SSRI/SNRI treatment. (Remember that the serotonin transporter is the target of serotonin uptake inhibitors)

A 6-week randomized controlled trial of 201 patients with major depressive disorder was performed. Subjects were given paroxetine 20-40 mg/d (SSRI), fluvoxamine 50-150 mg/d (SSRI), or milnacipran 50-75 mg/d (SNRI). Efficacy of the therapy was measured by comparing baseline Hamilton Depression Rating Scale (HAM-D) values with those from the end of the 6 week treatment period. Genomic DNA was gathered from each patient and sequenced so that SLC6A4 mutations could be analyzed. 32 variants were found, and 17 of these were new polymorphisms. One of the polymorphisms, rs3813034, resulted in significantly altered HAM-D scores for each medication administered, suggesting it has an effect on SSRI/SNRI response.

Considering all the treatment hurdles those with depression face (medications take a lot of time for effects to be realized and they may not be effective for many people), I think it is important to research the pharmacogenetics involved with SSRIs. This can help create more individualized treatments for patients who do not have months to spend time putting their well-being on hold while they try numerous antidepressants before finding one that works. Do you think it would be practical and possible to someday have a genotype-based protocol for antidepressant treatments?

Nonen, S et al. Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder: Sequencing Analysis of SLC6A4. J. Clin. Psychopharmacol. 2016; 36(1):27-3.

Urine Drug Screens: Considerations for the Psychiatric Pharmacist

This study was a literature review that investigated prescription medications, psychiatric medications in particular, that can cause false positives in urine drug screens UDSs). The authors also investigated some data on consumer products used to produce false negative UDSs. Besides prescription/ OTC medications and dietary supplements/ masking agents, there are other factors that can affect the accuracy of UDSs. These other factors include how long and how much someone has been using the substance, pharmacokinetic profile of the substance and its metabolites, and nature of the urine sample (pH, urine creatinine levels, temperature).

The most commonly UDSs are immunoassays that examine drug-specific antibody activity at specific concentration levels. The standard 5-panel tests (typical test used for job drug-testing and used in hospital laboratories) screen for amphetamines, cocaine (and metabolites), opiates, marijuana (and metabolites), and phencyclidine. There are more labor-intensive and accurate tests available (gas chromatography–mass spectrometry, for example), but the immunoassay-type UDS is most commonly used.

The study identified 14 articles that found psychiatric medication- associated false positive UDS results, 10 of which were antidepressants and 4 of which were antipsychotics medications. Phenothiazine antipsychotics, bupropion, trazadone, selegiline metabolites, as well as some OTCs (products containing dimethylamylamine, ephedrine, phenylephrine, and pseudoephedrine) were associated with inaccurate UDS results. There was no evidence supporting false positive results for cocaine from psychiatric medications. UDSs for opiates are qualitative in nature and are not very specific, meaning that the type of opioid is not easily determined through the immunoassay screen. For example, someone taking codeine may test positive for morphine. In regards to psychiatric medication- associated false positives, chlorpromazine, thioridazine, and clomipramine may have cross-reactivity for methadone. There were no psychiatric medications associated with false positive results for marijuana UDSs. Synthetic cannabinoids (medical marijuana), however, can theoretically produce false positive results, and dronabinol and nabiximol have been shown in the literature to do so. For phenylcyclidine, thioridazine and venlafaxine and its metabolite have been associated with false positive UDSs. This article also cited a review that found several commercially available and OTC products that can affect the accuracy of UDSs, causing false negative results. These products frequently contained either glutaraldehyde, nitrite, pyridinium chlorochromate, or peroxidase and peroxide.

Both false positive and false negative UDS results can negatively impact patient outcomes. Patients taking some of these psychiatric medications may be falsely accused of using substances and may face unfair removal from drug treatment programs or lose child custody and social support. Likewise, false negative results obtained by using masking agents may prevent the patient from getting proper treatment and diagnoses. Pharmacists can be aware of these potential inaccuracies (considering the connection with psychiatric medications) and educate healthcare colleagues to critically evaluate results of immunoassay UDSs, especially if the results can have major consequences for the patient. In this way, I think that psychiatric pharmacists can be patient advocates.

Mental Health Clinician. 2016;6(1):42-47

Disopyramide for Hypertrophic Cardiomyopathy: A Pragmatic Reappraisal of an Old Drug

I found out about this article through a P4 student who was preparing for a case presentation on rotations. I was pleased to realize that the topic relates to our current anatomy and physiology material and even more so that Dr. Coons authored it!

This article evaluates the use of disopyramide in patients with hypertrophic cardiomyopathy (HCM). Before jumping into how disopyramide works and whether it’s effective (topic of the article), I’ll give some basic background information on the disease state. Hypertrophic cardiomyopathy sounds like a mouthful, but it’s essentially an inherited disease of the heart muscle (myopathy) in which the muscle is enlarged/ thickened (hypertrophic) for no apparent reason. If you remember from the anatomy and physiology lectures, thickened heart muscle can lead to a lot of problems. It makes it more difficult for the heart to work efficiently as the thickening decreases elasticity. About 1 in 500 people have this condition, and about two thirds of those with HCM have obstruction of the left ventricular outflow tract (LVOT). This obstruction occurs when the ventricle contracts and drag force pushes the mitral valve leaflet toward the septum. HCM is typically treated with ß blockers or verapamil, and for those with particularly bad cases that don’t respond to medication therapy, surgery is an option. There is another therapy, however, that has been proven to be effective and safe in those with HCM and LVOT obstruction– disopyramide.

Disopyramide is a class 1A antiarrhythmic, but it can be used off-label as treatment in patients with HCM with LVOT obstruction who do not respond to ß blockers or verapamil. This drug works by slowing phase 0 of the cardiac muscle action potential (remember phase 0 is the opening of sodium channels and rapid influx of sodium). Thus it has strong negative inotropic activity (weakens the force of heart contraction) which slows the outflow from the left ventricle which delays or eliminates the mitral-septal contact responsible for obstruction. A review of 3 clinical studies shows that disopyramide improves heart failure symptoms and reduces the need for surgery in those with HCM and LVOT obstruction who don’t respond to ß blockers or verapamil. There are some concerns with this therapy, however. Its pharmacokinetics are interesting– it has nonlinear, saturable protein binding meaning that it’s hard to predict concentrations of free disopyramide given small increases in plasma concentrations. With this in mind, dosing and monitoring in a hospital setting is important when administering disopyramide. Anticholinergic effects and pro-arrhythmias can occur if therapy is not carefully managed.

While we haven’t covered this disease state nor antiarrhythmics in detail in class, I was glad that I could use my current knowledge to better understand disopyramide and HCM. It’s interesting to see how the conceptual groundwork laid in anatomy and physiology and principles of drug action paves the way toward understanding more complex issues. One thing unclear to me, however, is how a drug like disopyramide can have anticholinergic adverse effects. How does the slowing phase 0 of cardiac action potentials relate to the parasympathetic system?

Verlinden N. J., Coons J. C., Pharmacotherapy. Disopyramide for hypertrophic cardiomyopathy: a pragmatic reappraisal of an old drug. 2015; 35:1164-72