Instructor: Sandy Andrews, CPhT
Feeling blue is something we all have experienced at some point in our lives. The daily chores of life can become monotonous and, in some cases, far too overwhelming. Some days you just can't seem to get a break. One too many days like this and it is easy to understand how depression can creep into our lives. The Centers for Disease Control and Prevention (CDC) estimates that depressionaffects nearly 19 million adults or approximately 10% of the US population. The facts about depression in the US become quite startling the more we begin to uncover and discover about this disease. While nearly twice as many women will be diagnosed with depression, it is believed just as many men suffer from the effects of the disease. Why does depression go undiagnosed in so many men? The answer to this question may not be conclusive, but researchers believe it is partly because men are less likely to seek medical attention for their symptoms. According to a Harvard Medical School publication entitled Recognizing Depression in Men, 10-17% of men will experience the symptoms of depression at some time in their life. The publication continues by relaying that four times as many men commit suicide due to the symptoms associated with depression than women, however, men with depression are not just at increased risk for suicide. Men that have been diagnosed with depression or symptoms associated with depression are also more likely to be affected by coronary artery and cardiovascular disease. With increased risk factors such as these, it is not difficult to understand why there is such a push in the medical community for the early diagnosis and treatment of depression in men. So what makes depression in men different than depression in women? In reality, the disease state does not truly alter from men to women, but how the symptoms present themselves may vary. In fact, the symptoms men generally display with depression are often times the polar opposite of the symptoms women generally display. Men that are diagnosed with depression will often feel anxious or restless, whereas women often feel lethargic or listless. Other symptomatic differences between men and women might include weight loss for men, but weight gain for women, diagnosis of obsessive-compulsive disorders for men, but diagnosis of anxiety disorders for women. However, one of the most alarming differences demonstrated is the increased risk men have for developing alcohol or substance abuse as a result of their depression. Symptoms Typical of Men and Women Symptoms More Typical of Men Feelings of sadness, loneliness, worthlessness, despair or general unhappiness Loss of interest in hobbies or things that once brought interest or pleasure Agitation or feelings that spark irritability Noticeable weight loss, weight gain, or decrease or increase of appetite Headaches, digestive issues, chronic pain or other symptoms that are displayed as a physical problem Inability to sleep or sleeping too much Excessive issues with sleeping patterns Feelings of exhaustion, powerlessness, weakness Sudden changes in behavior including need to control or abusiveness that often times leads to violence Loss of energy or feeling of excessive tiredness Alcohol or substance abuse often as an intent to hide the symptoms of depression The symptoms of depression can be treated, but men more than women oftentimes fail to seek treatment. Some of the reasons for this may lie in the stigma some men may feel when admitting they need to seek help for their symptoms. For some men, admitting that they may be depressed could be interpreted as a sign of weakness, particularly if they are in a position of authority or hold a high position within their company. Fortunately, through the efforts of the medical community this stigmatism of weakness is slowly being eroded away. There are a variety of treatment options for depression. A treatment regimen might include counseling with a licensed professional, changes to diet and exercise, medication or a combination of the above therapies. Antidepressants are the classification of medications used to treat depression in both men and women. There are five sub classifications of antidepressants: selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and a category known as other, because they do not fall into any of the aforementioned categories. Selective Serotonin Reuptake Inhibitors (SSRIs) Serotonin and Norepinephrine Reuptake inhibitors (SNRIs) Tricyclic Antidepressants (TCAs) Monoamine Oxidase Inhibitors (MAOIs) Other Lexapro (citalopramin) Prozac (fluoxetine) Celexa (citalopram) Luvox (fluvoxamine) Zoloft (sertraline) Paxil (paroxetine) Brintellix (vortioxetine) Effexor (venlafaxine) Pristiq- (desvenlafaxine) Cymbalta (duloxetine) Fetzima (levomilnacipran) Elavil (amitriptyline) Norpramin (desipramine) Sinequan, (doxepin) Tofranil (imipramine) Pamelor (nortriptyline) Vivactil (protriptyline) Surmontil- (trimipramine) Nardil (phenelzine) Parnate (tranylcypromine) Marplan (isocarboxazid) Eldepryl (selegiline) Wellbutrin (NDRI) (bupropion) Desyrel (Not a true SSRI) (trazadone) Selective Serotonin Reuptake Inhibitor (SSRIs) is one of the largest classifications of prescription drugs used to treat depression. SSRIs work by blocking the production of a neurotransmitter of the brain called serotonin. Serotonin, a chemical messenger that is produced primarily in the brain, is responsible for any number of communication duties throughout the body's neurology system. In fact, most of our brain cells, and there are approximately 40 million, have some kind of contact with serotonin. Serotonin affects everything from memory, learning, and mood to appetite, sleep, and sexual desire. Serotonin not only affects emotional and cognitive responses, but bodily functions as well. Body temperature regulation, cardiovascular function, muscle function, and endocrine function are all affected by serotonin's ability to communicate with the brain. Given these facts it is not hard to understand the substantial role serotonin plays in our mental and physical well-being. Knowing the value of serotonin gives us a much clearer picture of how SSRIs assist the body and mind when fighting the symptoms of depression. All SSRIs work along the same premise, blocking the reuptake of serotonin in order to boost the cells that control mood in our brain. When these cells get a kick from serotonin our mood is lightened and we see the world in a little better light. However, as useful as serotonins are in boosting our moods, they are not without side effects that may cause some mild concern. When understanding and evaluating the side affects associated with SSRIs we need to recall the job duties of serotonin. SSRI therapy for depression may cause, dizziness, insomnia, weight gain or weight loss, nervousness, headache, vomiting, diarrhea, and erectile dysfunction in men. Side effects associated with SSRIs such as headache, insomnia, and erectile dysfunction, can sometimes be the limiting factor that keeps men from seeking treatment for depression. Unfortunately, when this is the case, the problem goes on untreated, an in most cases, becomes increasingly worse. Serotonin Norephenephrine Reuptake Inhibitors (SNRIs) are a second classification of drugs that treat the symptoms of depression. As one might guess, SNRIs work by blocking the absorption of serotonin and norephenephrine neurotransmitters in the brain. When these two chemical communicators are increased in the brain, mood becomes elevated and depression symptoms become less pronounced. Researchers have found that not only do SNRIs assist in alleviating the symptoms of depression, but in some cases, pain as well. SNRIs like Pristiq (desvenlafaxine), Cymbalta (duloxetine), Savella (milnacipran), and Effexor (venlafaxine) have also been proven to be effective in controlling chronic nerve pain in certain disease states. Back pain associated with nerve damage, peripheral neuropathy, fibromyalgia, as well as osteoarthritis have all had positive results when treated with SNRIs. Scientists have not been able to unequivocally determine the mechanism or reason behind SNRIs success in treating pain, but again, the links seem to be the increase of serotonin and norepinephrine SNRIs initiate. Some of the side effects associated with SNRIs include, but may not be limited to, nausea, dizziness, dry mouth, feeling of always be tired, or excessive sweating. SNRIs may also cause chronic constipation, difficulty urinating, agitation, or headache. Not all patients will experience side effects from SSRIs or SNRIs, but if symptoms do arise it is recommended that patients speak with their physician or pharmacists in order to gain a greater understanding of their drug therapy and the side effects they may cause. Fortunately, most symptoms associated with SSRIs and SNRIs will become less pronounced as the therapy continues. Tricyclic antidepressants are the earliest classification of antidepressants available to the public. Discovered in the early 1950's and made available to the public as a prescription drug in the middle part of the 1960's, tricyclic antidepressants are considered to be part of what is known as the golden decade of psychopharmacology. Tricyclic antidepressants are based upon a three-cycle affect. Tricyclic increase the amounts of serotonin and norepinephrine, two neurotransmitters scientist believe are responsible for elevating mood, and block the affects of acetylcholine, a neurotransmitter within the central and peripheral nervous system. As norepinephrine and serotonin increase and elevate mood, acetylcholine is blocked, which also assist in elevating mood. Although scientists may not have realized it when they discovered tricyclic antidepressants in the 1950's, a research study conducted by Dr. Marina Picciotta, a researcher at Yale University has established a link between acetylcholine and depression. Dr. Picciotta's team contends that abnormally high levels of acetylcholine may be the root cause of depression. According to the 2013 research report, lab mice which had high levels of acetylcholine exhibited symptoms of depression much more often than lab mice with normal levels of acetylcholine. Part of the reason for this can be contributed to a neurotransmitter by the name of acetyl-cholinesterase or more commonly AChE. AChE helps to lower acetylcholine levels, which in most people, helps to stabilize mood and allows serotonin and norepinephrine to be produced. The result of Dr. Picciotta's research seems to conclude that high levels of acetylcholine, rather than low levels of serotonin are most likely responsible for depression. If we can understand the root cause of a disease state we are much more likely to understand how to approach treatment. Unknown to researchers in the early 1950's acetylcholine appears to play a much greater role in depression than first thought. Tricyclic antidepressants, as previously mentioned, were some of the first antidepressants available to the public. Tricyclic antidepressants are still used today, but not as commonly as SSRIs or even SNRIs. Tricyclic antidepressants may also be used to treat obsessive compulsive disorder and even bed wetting, as well as some off label disease states, such as panic disorder, chronic pain associated with migraine or back pain, and even premenstrual syndrome. Available tricyclic antidepressants include, Elavil (amitriptyline), Norpramin (desipramine), Sinequan (doxepin), Tofranil (imipramine), Pamelor (nortriptyline), Vivactil (protriptyline), and Surmontil (trimipramine). Some of the side effects associated with tricyclic antidepressants include, blurred vision, dry mouth, constipation, low blood pressure on standing, possible rash or hives as well as the possibility of increased heart rate. Tricyclic antidepressants have also been known to increase urinating difficulties, as well as worsening narrow angle glaucoma. It is also recommended that tricyclic antidepressants not be used in conjunction with monoamine oxidase inhibiting (MOI). Although tricyclic antidepressants were some of the first antidepressants on the market, they were not the first. The first antidepressants on the market were monoamine oxidase inhibitors or MOAIs. MOAIs are rarely used today, mostly due to the advent of better antidepressant classifications like SSRIs and SNRIs. While tricyclic were first discovered in the early part of the 1950's they never really hit the US market until middle part of the 1960's. MOAIs on the other hand have been on the US market since the early part of the 1960's. MOAIs work by blocking an enzyme known as monoamine oxidase. Monoamine oxidase is an enzyme in the brain that breaks down the production of serotonin, dopamine, and epinephrine. As we have already learned, when serotonin is blocked or disrupted it decreases the production of serotonin the brain used to regulate responses specific to the neurotransmitter serotonin, like mood and emotions. The list of available MOAI drugs available in the United States includes, Nardil (phenelzine), Parnate (tranylcypromine), Marplan (isocarboxazid), and Eldepryl (selegiline). It should be noted that while Eldepryl (selegiline) is classified as an MOAI antidepressant drug it has also had success in treating the symptoms associated with Parkinson's disease. Used in combination with Sinemet (carbidopa/levodopa), Eldepryl (slegiline) has been useful in decreasing tremors associated with Parkinson's disease, as well as improving some range of motion. MOAIs are rarely used today, although some researchers believe MOAIs are still quite effective in combating the symptoms of depression, especially when they are used in conjunction with specific SSRIs or SNRIs. However, MOAIs come with a long list of side effects. A few examples of MOAI side effects includes, sudden drop in blood pressure upon standing, weakness, dizziness, fatigue, increased anxiety, headache, agitation, weight and impotence. One other significant warning associated with MOAIs carries a FDA Black Box Warning. MOAIs must carry a FDA Black Box Warning due to their increased risk for suicidal behavior when used to treat teenagers and young adults for depression. Additionally, the FDA warns against using MOAI with certain other antidepressants such as, Paxil (paroxetine), Prozac (fluoxetine), Elavil (amitriptyline), Pamelor, (nortriptyline) and Wellbutrin (bupropion). Other drugs that may have major interactions with MOAIs include, methadone, tramadol, meperidine, dexamethasone, St. John's wort, cyclobenzaprine, and mirtazapine as well as the seizure drugs, Tegretol (carbamazepine) and Trileptal (oxcarbazepine). Finally, it is recommended that pseudoephedrine, phenylephrine, epinephrine, or phenylpropanolamine not be used when taking a drug therapy that includes MOAIs, particularly for those who have been diagnosed with high blood pressure as these drugs may increase the risk for an acute hypertensive episode. It is recommended that patients take extreme caution when taking MOAIs as the drugs listed above may lead to serotonin levels that are alarmingly high, which could lead to confusion, high blood pressure, hyperactivity, tremors, coma, or possibly even death. Patients that may be contemplating a treatment that includes an MOAI should consult their physician or pharmacist. The next sub classification of antidepressant is known as Norepinephrine Dopamine Reuptake Inhibitor (NDRI), and currently the only drug available within this sub classification is Wellbutrin (bupropion). Wellbutrin (bupropion) works by blocking the reuptake of norepinephrine and dopamine, so more of the neurotransmitters can remain in the brain and assist in maintaining emotional responses. Wellbutrin (bupropion) is also used to treat Seasonal Affective Disorder (SAD); a depression order that manifests during the seasonal changes, in addition to being used as part of smoking cessation therapies. Wellbutrin (bupropion) may also be used to treat anxiety disorders as well as Obsessive Compulsive Disorder (OCD). Wellbutrin (bupropion) does not typically have the sexual side effects experienced with other antidepressants like SSRIs and SNRIs, but nonetheless it does come with some noteworthy therapy concerns. Wellbutrin (bupropion) has been known to bring on sudden seizure disorder, so patients that have a history of seizure should not take Wellbutrin (bupropion). Use of Wellbutrin has also been linked to, heart disease, blood pressure, narrow angle glaucoma, diabetes, kidney and liver disease. Patients that take Wellbutrin (bupropion) may experience agitation, dry mouth, insomnia, nausea, constipation, or tremor. Patients taking Wellbutrin (bupropion) should not crush or split Wellbutrin (bupropion) as crushing or splitting the tablet will damage the drug's mechanism. If a dose is missed, then the patient should not double their daily dose, but rather skip the dose till the next scheduled dose. Patient taking Wellbutrin (bupropion) should also avoid drinking alcohol as it has been proven to increase the risk for seizures. One final antidepressant that should be explored is Desyrl (trazadone). While Desyrl (trazadone) does work by increasing serotonin levels in the brain, it is not a true SSRI and cannot really be placed within this sub classification. Desyrl (trazadone), which is also used as a sleeping aid, should not be used with MAOIs. Patients should not take Desyrl (trazadone) if they have taken an MAOI within the last 14 days. Touted as an old school antidepressant, Desyrl (trazadone) is one of the earliest antidepressants on the US market. But as useful as it can be to some people it can be just as dangerous to other. Some side effects associated with Desyrl (trazadone) therapy include, but may not be limited to, heart disease, liver or kidney disease, seizures or epilepsy, and narrow angle glaucoma. Desyrl (trazadone) should not be given to children and should be prescribed with caution in adolesants and young adults. The first step in treating depression is recognizing the symptoms. The National Institute of Mental Health (NIMH) has initiated a campaign targeted specifically to men and the undiagnosed symptoms of depression. The website, http://www.nimh.nih.gov/health/topics/depression/men-and-depression/, shares stories of men that have been diagnosed with depression as well as useful publications, possible symptoms and treatment options. The site encourages men that feel they may have the symptoms of depression to seek immediate treatment from their physician. Research has shown that while depression can affect anyone, men who have depression are often very reluctant to seek the help they need. The social stigmatism of a depression diagnosis or fear of the side effects associated with some depressant treatments often keep men from receiving the help they need. Depression where it be diagnosed in a man or a woman is a disease state and should not be abused by social stigmatism. Often times it is the lack of understanding that keeps people from seeking the help they need. Antidepressants, while being able to do a great deal of good, can still have some very alarming side effects. Pharmacy technicians aware of the symptoms of depression may help to alert the pharmacist to patients that need additional counseling or may have the potential for serious medication interactions. While pharmacy technicians may never give advise or information regarding medications to patients, being able to identify those who may be taking drug therapies that interact with antidepressants, or patients that may have questions regarding their therapy, but are too ashamed to ask for help, can be the first and often the most useful step in assisting patient with drug therapies. References: Bouchez, C. Serotonin: 9 Questions and Answers, WebMD.com, 10/2011, http://www.webmd.com/depression/features/serotonin?page=3 accessed 28 October 2014 Centers for Disease Control and Prevention, Depression, 2014, http://www.cdc.gov/Depression.html, referenced 22 April 2014 Cherry, K. What is Acetylcholine?, About Psychology, 10/2014, http://psychology.about.com/od/aindex/g/acetylcholine.htm, referenced, 29,October, 2014 Drug Information Handbook, American Pharmacists Association, Antidepressants, Lexicomp, 2013 Harvard Health Publications, Recognizing Depression in Men, 2011, http://www.health.harvard.edu/mentalextra, referenced 23 April 2014 Mayo Clinic, Diseases and Conditions, 2014, http://www.mayoclinic.org/diseases-conditions/depression/in-depth/male-depression/art-20046216, referenced 22 April 2014 National Institute of Mental Health, Men and Depression, http://www.nimh.nih.gov/index/shtml, referenced 23 April 2014 Shukla, S. Uncovering the Biochemical Basis of Depression, Yale Scientific Magazine, 05/11/2014, http://psychology.about.com/od/aindex/g/acetylcholine.htm referenced, 29 October 2014 Substance Abuse and Mental Health Services Administration, Self-Assessment Program, Men and Depression, 2014, http://www.mentalhealth.samhsa.gov/databases/, referenced 22 April 2014 Phillips, S. Men and the Hidden Dangers of Depression, This Emotional Life, Public Broadcasting Services, 2009, http://www.pbs.org/thisemotionallife/men-and-the-hidden-dangers-of-depression, referenced 24 April 2014 Potential Root Cause of Depression Discovered by NARSAD Grantee, Brain and Behavior Research Foundation, 04/13/2013, https://bbrfoundation.org/discoveries/potential-root-cause-of-depression-discovered-by-narsad-grantee referenced 29 October 2014