Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians

This study analyzed nonpharmacological versus pharmacologic treatment of adults with major depressive disorder. More specifically the study compared how treatments such as acupuncture, exercise, yoga, St.John’s wort etc.. worked compared to that of second generation antidepressants. Depressive disorders are a growing concern in the health community since it affects a broad range of patients. In recent years more has been done to try to educate others on depression and possible treatments. The study was done by collecting randomized controlled trials through the years of 1990 through September 2015. The study utilized several databases to find appropriate studies that fit into the desired criteria. After comparing multiple studies, the data concluded that clinicians should choose between cognitive behavioral therapy or second generation antidepressants. The major point was made that the therapy should be picked based on the patient’s lifestyle, desires, and needs.

 

After reading the study and the conclusion of the data I found it refreshing that there are ways to manage Major Depressive Disorder without the use of medications. While as pharmacist our whole business is drugs, but this doesn’t mean we push unnecessary drugs onto our patients. As pharmacists we are obligated to provide the best possible information to patients in order to help them lead healthier lives. I think the big take away point it which therapy is more beneficial and which therapy is a patient more likely to stick with. If a patient is often considered with the possible side effects of antidepressants and doesn’t like the idea of taking a medication. Then if cognitive behavioral therapy has been shown to replicate the same outcomes as a medication then that would be the best course of action for them since they are more likely to stick with it. Overall, I think it’s important to remember that there are other options for certain disease states that require life style changes and may offer the same benefits as a medication.

 

http://annals.org.pitt.idm.oclc.org/article.aspx?articleid=2490527

 

Qaseem A, Barry MJ, Kansagara D, for the Clinical Guidelines Committee of the American College of Physicians. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice

Strategies to improve anxiety and depression in patients with COPD: a mental health perspective.

Chronic obstructive pulmonary disease (COPD) is a pulmonary disease characterized by progressive and potentially reversible symptoms.  In COPD, anxiety and depression are surprisingly common.  This article aimed to comment on the lack of literature of psychological disorders associated with COPD.  First, this study stressed that patients prefer to be treated by non-pharmacological means instead of drug therapy.  Individual and group therapy are useful in treating patients with COPD.  Most antidepressants work the same on depression but have different side effects based on drug class.  This article also stressed that one-third of patients suffering from anxiety and depression due to COPD are untreated.  It also states that one-third of patients with COPD have related anxiety and depression.  Despite all the research conducted by this article it was not able to provide a concise treatment plan but it did specify that mental illness is widely under-diagnosed and under-treated.

This article was interesting to me becasue it was a review article about a topic that I had heard about but had very little knowledge on the matter beforehand.  I heard of COPD but did not know there was such a high correlation between between depression and anxiety and COPD.  I was also curious to see that drug therapy was not the primary source of treatment for this disease state and it was instead preferred to treat using group and individual therapy.  Considering we rarely discuss that form of treatment it was interesting to see that as the principle treatment and learn more about it.

Tselebis A, Pachi A, Ilias I, et al. Strategies to improve anxiety and depression in patients with COPD: a mental health perspective. Neuropsychiatric Disease and Treatment. 2016;12:297-328 

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.

NSAIDs Are Associated with Lower Depression Scores in Patients with Osteoarthritis

This study looked at whether or not NSAIDs, as an addition to antidepressant therapy, could decrease depressive symptoms in patients with osteoarthritis.  The study was a multicenter, double-blind, placebo-controlled study with patients who have active osteoarthritis.  Each participant was put into one of three groups: placebo group, ibuprofen 800 mg (three times a day) or naproxen 500 mg (two times a day) group, or Celebrex 200 mg (one time a day) group.  The patients were tested for major depression using the standard health questionnaire-9 (PHQ-9) scale.  Each person was tested at baseline, after two weeks of treatment and after six weeks of treatment.

The results showed that all three groups had similar average PHQ-9 scores at the baseline screening and at the last screening, after six weeks of treatment.  However, there was a detectable difference in change of PHQ-9 score between the groups with the ibuprofen/naproxen group and the Celebrex group having lower scores of .31 and .61 respectively.

The study concludes that NSAID usage in patients with osteoarthritis shows a trend of reduction in depressive symptoms.  I, however, do not believe there was enough evidence in the trial to conclude this.  Additionally, I believe they mistook correlation with causation.  Each group, in addition to a decrease in depression, also saw a decrease in pain.  As we have learned in class, pain can cause depression.  So while NSAID usage may correlate with decreased depression, it may have to do with the pain relief and not the specific mechanism of action of NSAIDs.  To disprove this, NSAIDs should also be compared to other pain relievers with different mechanisms of action.

Rupa IL, Gandhi s, Aneja A, et al. NSAIDs Are Associated with Lower Depression Scores in Patients with Osteoarthritis. Am J Med. 2013;126(11).

http://www.amjmed.com/article/S0002-9343(13)00358-6/abstract

Antidepressant medication use and glycaemic control in co-morbid type 2 diabetes and depression

Depression is common in diabetes diagnosed patients and it also causes increased risk of hyperglycemia, morbidity, and mortality. A study was conducted to determine if the use of antidepressant medication is associated with glycemic control in depressed patients with type 2 diabetes.

This study was conducted using electronic medical record registry data of ambulatory primary care visits from 2008 to 2013. Relationship between ADM use (determined by prescription orders) and glycaemic control (determined from measures of glycated hemoglobin/ A1C) were studied. A good glycemic control was defined as AIC < 7.0%.  Good glycemic control was achieved by 50.9% of depressed subjects receiving ADM versus 34.6% of depressed subjects without ADM.

Although this relationship studied does not take into account adherence of medication, it still proves an interesting point; medication taken for a separate indication but relating to the primary disease state may help in patient drug therapy. It is important to not only look at the disease state and what medications are specific for that disease state, but also to view the broad picture. What else is the patient currently diagnosed with? Even if these disease states do not directly relate to the primary disease state, they could serve as clues into figuring out what is best for the patient.

Brieler J., Lustman P., Scherrer J., et al. Antidepressant medication use and glycaemic control in co-morbid type 2 diabetes and depression. Fam. Pract. 2016; 33: 30-6

The effect of dexamethasone on symptoms of posttraumatic stress disorder and depression after cardiac surgery and intensive care admission

Following cardiac surgery, patients are typically admitted to the intensive care unit (ICU) for a short period of time. Studies suggest that 14 to 25 percent of these patients develop posttraumatic stress disorder (PTSD) and 23 to 32 percent develop depression. Corticosteroids produced via the hypothalamus-pituitary-adrenal (HPA) axis bind to glucocorticoid and mineralocorticoid receptors and help patients adapt to changing environments. Therefore, it is thought that patients with reduced HPA axis activity may be less able to adapt to such changes.

Kok, Hillegers, Veldhuijzen, et al. studied the effect of dexamethasone on the prevention of PTSD and depression among 1,125 patients admitted to the ICU following cardiac surgery between April 2006 and November 2011. Dexamethasone is a synthetic glucocorticoid, which acts on glucocorticoid receptors (GR) to produce anti-inflammatory effects. Of the 1,125 patients enrolled in this study, 561 patients received 1 mg/kg dexamethasone intravenously. This dose was administered following the start of anesthesia and prior to cardiopulmonary bypass. The remaining 564 patients received placebo.

In their 1.5-year follow-up, the authors report similar numbers of patients with PTSD or depression between the treatment and control groups. Among patients who received dexamethasone, 52 patients and 69 patients developed PTSD or depression, respectively. In comparison, 66 patients who received placebo had PTSD and 78 had depression at the time of follow-up. Overall, these results suggest that intraoperative administration of 1 mg/kg dexamethasone has no effect on patients’ likelihood of developing PTSD or depression following ICU discharge. However, dexamethasone was found to have a positive effect on female patients, reducing the prevalence of these psychiatric conditions in this subgroup.

Although this article specifically discusses the development of PTSD and depression following cardiac surgery, it is also applicable to other surgical procedures that require patients be admitted to the ICU. Therefore, this problem effects many patients we will see in the future as pharmacists. By suggesting that dexamethasone is not effective for the prevention of psychiatric conditions in patients following ICU discharge, the authors also demonstrate the need for further research for a solution.

Crit Care Med. 2016;44(3):512-20.

Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical serotonin/glutamate neurotransmission

In a novel study by Linge and colleagues, cannabidiol (CBD) was shown to exhibit strong anxiolytic and antidepressant effects in mice. The study also elucidated CBD’s mechanism of action on serotonin receptors in the brain. Their findings indicate that CBD could represent a novel fast-acting antidepressant drug.

CBD is the main non-psychotomimetic component of marijuana. This means that behind THC, the compound responsible for many of the mind-altering affects we collectively refer to as a “high,” CBD produces the majority of it’s therapeutic benefit without inducing highness. Utilizing the olfactory bulbectomy (OBX) mouse model of depression, researchers studied the behavioral efficacy of CBD via the enhancement of serotonergic and glutamatergic transmission through the modulation of 5-HT 1A receptors. Classical antidepressants act through similar serotonergic attenuation whereas the effects of fast-acting antidepressants seem to be mediated mainly by glutamatergic signalling.

The results of this study shows that CBD exerts rapid antidepressant-like effects as evidenced by the reversal of OBX-induced hyperactivity immediately after the first injection. Additionally, its efficacy is maintained and improved with the repeated administration, as anhedonia (inability to feel pleasure) was completely relieved after one week of treatment with a dose of 50 mg/kg. The findings also revealed a crucial role of 5-HT 1A and CB1 receptors in the behavioral and anxiolytic effects of CBD. As anxiety is a complex syndrome affected by different brain processes, the two receptors could be implicated in the anxiety outcome at different levels.

In summary, the fast onset of antidepressant action of CBD and the simultaneous anxiolytic effects, combined with the broad range for therapeutic dosage and the lack of psychotomimetic effects shows a strong therapeutic advantage for its use in clinical practice compared to other antidepressant alternatives.

Linge R, Jiménez-Sánchez L, Campa L, et al. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuopharmacology 2016;103:16-26

Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study

When prescribing medications for the initiation of  a new therapy in patients with multiple chronic diseases, physicians often look to guidelines to determine their recommended treatment option.  While this is considered good practice, it is important to not look at the disease state as a singular entity when choosing a therapy for the patient to follow due to the effects that certain conditions have on one another. This study looked to analyze the association between guideline recommended drugs and death in older adults with multiple chronic disease states. To do this, 8578 adults aged 65 and older were monitored though three years of treatment. Patients involved in the study had a variety of disease states including but not limited to atrial fibrillation, chronic kidney disease, depression, diabetes,  and hyperlipidemia. Results from the study showed that over 50% of the participants received guideline recommended drugs without the consideration of other disease states. Although 15% of the patients died during the course of the study, researchers were able to determine that cardiovascular medications were associated with a decrease in mortality. Other guideline medications analyzed in the study did not show an association with reduced mortality. Overall, it was determined that choosing medication therapy for patients should only be done after fully analyzing the patients other conditions.

I believe this study is important due to the fact that guideline recommended medications are commonly dispensed in the pharmacy setting. It is thus important for us to understand how guideline drugs interact with each other to protect a patient at the point of treatment initiation. By doing this, we will be able to avoid adverse drug effects that can result due to medication interactions. I believe that this is one of the most important roles of a pharmacist because it helps promote patient well-being and increases the likelihood of medication regiment adherence. The goal of our profession is to protect patients and advise them on how to find ways to live a healthy lifestyle. The easiest way to do this is by starting at the roots of the solution.

Tinoetti M, McAvay G, Trentalange M, et al. Association between guideline recommended drugs and death in older adults with multiple chronic conditions: population based cohort study. BMJ 2015; 351: h4984

Differences in prescribing psychotropic drugs for elderly with depression.

This study’s purpose was to address the prevalence of depression and inadequacy it is treated in most cases.  It analyzed the different types of drug classes that are prescribed to elderly patients.  A random sampling of 5% of inpatients was selected from the NHI in Taiwan.  Of the 5%, 1058 were geriatric patients with some form of mental depression.  The prescribing patterns were examined and compared.  Some of the most commonly prescribed psychotropics were: antidepressants (71.4%), anxiolytics (62.6%) and hypnotics (51.4%).  Varying types of medications were prescribed and it depends on the the type of medical professional.  This study concluded psychiatrist generally prescribe newer antidepressants than other physician specialties.

This article is interesting because it discussed the varying types of drugs that are prescribed.  It shows that there is a difference between the types of medications prescribed based on the type of specialty instead of having a standard that all prescriptions is based off of.  I believe that this is bad for the healthcare industry and could lead to problems across the industry.

Huang YC, Wang LJ, Chong MY.  Differences in prescribing psychotropic drugs for elderly with depression. Acta NeuroPsychiatry. 2016; 22: 1-8.

Duration of diabetes and its association with depression in later life: The Health In Men Study (HIMS).

This study compared the diagnosis of diabetes and it’s relationship to depression in men.  It was a cross-sectional study of 5462 men between the age of 70-89 years old.  The rate of these men’s depression was based on the Geriatric Depression Scale and diabetes was measured with fasting blood glucose levels.  There is a “J-shaped” curve relationship between depression and age with men with diabetes.  That means that depression increases as the men get older.  Although some other factors most likely play a pivotal role.

I was interested in this article because these disease states are treated by medications that pharmacists deal with on a daily basis.  To me, this emphasizes the importance of the pharmacist role in patient’s lives.  The better the patient’s diabetes is managed, the better their related depression might be treated.  if the diabetes is under control, the depression will not occur hopefully and therefore, there will not be a need for additional medical treatment.  The less medication needed, the better the life of the patient.

Almeida OP, McCaul K, Hankey GJ, et al.  Duration of diabetes and its association with depression in later life: The Health In Men Study (HIMS). 2016; 86: 3-9