Final Essay

 

Savannah Milam

BASIS Scottsdale Senior Project

May 4, 2012                            The Efficacy of Antidepressants

This study examines the effectiveness of antidepressants to treat major depression, a serious condition that affects 15 million Americans age 18 and older (approximately 6.7 percent of the U.S. adult population). Through a review of literature surrounding controversial antidepressants, it was determined that the treatment of depression is a complex subject, including philosophical, psychological, and biological components. This study discovered that one could not simply examine the standard definitions of depression and of its medication treatment options. In order to best comprehend whether a treatment for a mental illness like depression is effective, it is important to consider the possible causes of depression. From there, the value of each treatment must be considered on an individual, relative and diagnostic basis while comparing the resulting plan with current statistics in order to properly weigh the risks and rewards of antidepressant treatment.

This study found that the typical ideal treatment for a basic case of major depression is a combination of both antidepressant treatment and psychotherapy. The benefits of this combination most likely result from the treatment of both biological and psychological triggers for depression. Additionally, the combination of psychotherapy with antidepressant medication can result in more effective treatment of children and severe depression cases. In the end, the study concluded that antidepressants are more helpful than placebos in general, and are even more effective in combination with therapy.

The first step to understanding the efficacy of any treatment method is to understand the condition and its symptoms. Major depression is a mental illness characterized by the National Alliance on Mental Illness by the following symptoms:

“little interest or pleasure in doing things, feeling down, depressed or hopeless, trouble falling or staying asleep or sleeping too much, feeling tired or having little energy, poor appetite or overeating, feeling bad about yourself, that you are a failure or have let yourself or your family down, trouble concentrating on things, such as reading the newspaper or watching television, moving or speaking so slowly that other people could have noticed or the opposite in that you are so fidgety or restless that you have been moving around a lot more than usual [and] thoughts that you would be better off dead or of hurting yourself in some way"

If these symptoms persist for a period of more than two weeks, sufferers are instructed to seek the help of a doctor. What causes these symptoms is currently unclear. There is no single thing that medicine has determined as the cause for depression. It is most likely that depression is a combination of biological and environmental factors that lead to the development of negative symptoms. A basic example of an environmental factor that might trigger depression is the loss of a loved one. Depression is also genetically pre-disposed (ScienceDaily 2012). The biological triggers are more controversial.

            There is a theory that argues that depression is partially caused by a deficiency of certain neurotransmitters in the brain. This is best known as the monoamine deficiency theory of depression. Monoamines are the neurotransmitters that are claimed to be deficient, including serotonin, norepinephrine, and dopamine. These chemicals do extensive and complicated work in the body as a whole but some studies have suggested a strong correlation between depression and a deficiency of these chemicals in the brain (Nauert 2012). Could this be the only cause of depression? Critics of the monoamine deficiency theory claim that is unlikely and they are likely correct. There are studies available that strongly support what is often called the chemical imbalance theory. According to a study done by the Canadian-based Centre for Addiction and Mental Health (CAMH), monoamine oxidase A, an enzyme breaks down the neurotransmitters doctors claim to be lacking, is more prevalent in people with untreated depression than those who are not depressed (Meyer 2006). These patients may have less of the monoamines due to increased enzyme activity but if depression were as simple as a chemical imbalance then the efficacy of antidepressants would not be under attack as they would be sufficient as a treatment for the cause of the condition (Meyer 2009).
            To understand this, the next thing to examine is the way antidepressants function biologically. Antidepressants are believed to increase the concentration of certain neurotransmitters in the brain in a way beneficial to those suffering from depression. There are four major types of antidepressants. The neurotransmitter effects that they produce distinguish them all.  The oldest type of antidepressant is the monoamine oxidase inhibitor, abbreviated MAOI. The inhibition of monoamine oxidase keeps the oxidase enzyme from breaking down norepinephrine, serotonin and dopamine, which are believed to elevate mood (Ogbru 2012). Another type of antidepressant is the TCA, or tricyclic antidepressant. Tricyclic antidepressants increase the levels of norepinephrine in the brain and slightly increase the levels of serotonin as well (Ogbru 2012).  According to Psyweb.com, they are called tricyclic because of their chemical structure, but there are some tetracyclic antidepressants looped into the same group. TCAs work by blocking the reuptake of the two neurotransmitters they affect, resulting in an increased concentration of them in the synapse. Then there are selective serotonin reuptake inhibitors (SSRIs) that solely increase the levels of serotonin in the brain (NIH 2012). They are the most popular antidepressant because they have the least side effects and drug interactions (Daily Mail 2012). The newest antidepressants are the serotonin norepinephrine reuptake inhibitors, which increase both serotonin and norepinephrine levels and are abbreviated SNRIs (Mayo 2010a).

            These medicines typically increase the concentration of the neurotransmitters by affecting either the enzymes related to the chemical or the reuptake of the chemical by neurons. When the enzymes are affected, as in MAOIs, the enzymes are prevented by the medicine from breaking down or clearing away the chemicals in the synapses between the neuron cells of the brain (Ogbru 2012). In the case of a reuptake inhibitor, after a neuron releases neurotransmitters into the space between the original neuron and another neuron, that original neuron attempts to restore it's stock of that neurotransmitter by reuptaking some of the neurotransmitters it released. However, when the medicine is active, the reuptake is limited (NIH 2012). The goal of this is to increase the amount of neurotransmitter in the synapse for a longer period of time, making it more likely for adjacent neurons to receive the chemical message that the transmitters are meant to provide.

            If it were enough to alter the concentration of these monoamines in the brain, then it would follow that antidepressants would be extremely effective. However, this is not always the case. According to UpliftProgram.com, “antidepressants work for 35 to 45% of the depressed population." Only a fraction of the depressed patients who take antidepressants are relieved of their symptoms. In clinical trials, antidepressants often only match or slightly outperform placebos (Lakoff 2012). Clearly, this treatment is inadequate but that does not mean it is completely ineffectual.

            Depression has been described as poised to be “the second largest killer after heart disease by 2020 -- and studies show depression is a contributory factor to fatal coronary disease" (Uplift 2012). According to one site, "over 15 million people in the United States [are] suffering from depression" (Depression Stats 2012). Major depression is a common condition. The psychological nature of the condition often makes it easy for society to underestimate the disease, however, this cannot be mistaken for a personal weakness. This is a disorder that can result in death. No treatment method that can potentially safely prevent those deaths should be too hastily discarded. The question is not whether antidepressants are perfect but whether they are worth the risk of the side effects they produce and the possibility of their failure in order to potentially alleviate symptoms.

            This is a value judgment that must be made practically for antidepressants to be allowed on the market but it is also a judgment that relies on doctor evaluation of individual patient situations. The effectiveness of antidepressants is dependent on attentive prescription, responsible consumption, and detailed consideration of individual cases.  For this reason, to illustrate the conclusions of this study, hypothetical patients will be presented. These patients are not meant to resemble actual people. They simply present possible occurrences based on the documented effects of antidepressant treatment.

            The first patient will be called John. He is forty-one and dissatisfied with his job status. John’s family doctor has diagnosed him with major depression after John took a detailed survey called the PHQ-9, created to diagnose depression (Lalani 2012). His doctor was prompted to give him this survey after he complained of lethargy at a routine checkup. John’s symptoms illustrate a textbook case of major depression that would likely be classified as moderate in nature. He respects the decisions of his doctor and when she suggests he try an SSRI antidepressant known as fluoxetine (brand name Prozac), he agrees (NIMH 2012). She gives him a brief overview of the risks of some common side effects like nausea, insomnia, and loss of appetite (NAMI 2012). She also suggests he seek counseling for his depression in addition to his medication. He is provided with a list of nearby psychologists who accept his insurance. When John gets home, he discusses the diagnosis and treatment with his wife briefly. They decide not to spend money on therapy. He begins taking the antidepressant the next day.

            The second patient is twenty-five year old Jane. Jane was previously engaged to her college sweetheart. She is working as a receptionist at a hotel, attempting to rise in the ranks of the hospitality business. Jane has recently attempted suicide. The hospital where she is treated for suicidal drug overdose sends an on-call psychiatrist to assess her situation. Jane admits to the psychiatrist that she was devastated by her ex-fiancée’s decision to break off the engagement. She also mentions that she feels personally attacked by customer complaints at work. Jane owns that she knew herself to be depressed but was skeptical of the treatment options for depression. The psychiatrist prescribes sertraline, also known as Zoloft, an SSRI antidepressant, due to its low toxicity in overdose compared to other options for Jane’s severe depression (Daily Mail 2012) (NIMH 2012). The doctor also refers her to a counselor and Jane agrees to go. She begins taking the antidepressant the next day.

            The third patient will be known as Jessie. Jessie is a seven-year-old girl in remission from leukemia. She has cultivated a great fear of death and is already in therapy. Her therapist suggests that she is depressed after her negative thoughts persist. Jessie is referred to a child psychiatrist who prescribes the SSRI, Citalopram (NIMH 2012). Jessie’s psychiatrist schedules a follow-up appointment to be held once the prescription runs out in a month (Harris 2011).
            All of these patients have been prescribed an SSRI to start. This is because SSRIs are considered a safer option for a variety of reasons including lower toxicity, less drug interactions, and less side effects (Daily Mail 2012). The side effects of an SSRI, according to the Mayo Clinic, include nausea, dry mouth, headache, diarrhea, anxiety, sexual dysfunction, rash, increased sweating, weight gain, appetite loss, drowsiness or insomnia (Mayo 2010b). Obviously, some of these symptoms seem paradoxical. These are the side effects that are most common, do not always occur together and often disappear over time. However, SSRIs have other more serious side effects and reactions. They are typically not safe to take while pregnant. They can interact with other drugs, especially blood-thinning medications. If they interact with other drugs that also increase serotonin levels, they can produce serotonin syndrome, which is potentially fatal (Mayo 2010b). SSRIs also can induce increased suicidal tendencies and mania (Breggin 2008). These two side effects can destroy lives and should be taken very seriously. The tendency to suicide increases in children taking these drugs (NEJM 2004). The side effects of any medication, including antidepressants, can be a scary thing but they do not necessarily indicate enough risk to render the drugs ineffective on the whole.

            Within the first week of John’s treatment, he notices extreme insomnia and anxiety. He begins to steal packets of gum when he purchases gas for his car. He discusses quitting his job to his wife. She is alarmed but simply convinces him that they need the money. John is exhibiting symptoms of mania, a serious side effect that can result in what expert medical witness and doctor Peter Breggin calls “medication madness” (Breggin 2008). This mania, most likely caused by over stimulation from the antidepressant, will result in deterioration of John’s mental health and possibly of his physical wellbeing. As this continues, John’s decisions may escalate in risk to serious crime and or suicide. This symptom while noticeable is often difficult for loved ones and even doctors to attribute to medication right away, however, it occurs in varying degrees in approximately eight percent of people who take antidepressants (Breggin 2008). Serious side effects like mania make many people turn against antidepressants instinctively. While it is serious, this study has determined that the risk of these side effects (mania and suicide) is, on the whole, less than the possible reward of successful depression treatment.

            Jane starts attending cognitive-behavioral therapy. Her counselor insists that a contributing factor to her depression is low self-esteem. The counselor provides her with homework in the form of thought exercises meant to identify and correct irrational thought processes (Herkov 2012). For example, when Jane finds herself thinking that because her fiancée left, she will never be loved, she writes down the thought and identifies it as an exaggeration. Then she writes a more reasonable concept like “my fiancée wasn’t right for me but there are people out there who will value my qualities” (Hoffman 2012). Jane also takes her antidepressant as directed but in the first week she experiences unpleasant nausea. Jane seems to be benefiting from her counseling and she is taking her medicine responsibly. If she were to consult a doctor, he would most likely ask her to continue taking the antidepressant for four to eight weeks to see if the nausea subsides. Antidepressants are not an instant fix; they take time to become effective (Marano 2003).

            Jessie meanwhile begins taking her antidepressant but immediately feels anxious, nauseous and she has trouble sleeping. She tells her mother about these symptoms and they decide she should stop taking the medicine. When she tells her counselor about this decision at the end of the week, the counselor is alarmed and insists she meet with her psychiatrist early. Jessie may have found her medicine’s side effects intolerable but her decision to take herself off the medication was ill advised. Antidepressants are not addictive but they can cause unpleasant withdrawal symptoms that could match her previous side effects in discomfort (Hall-Flavin 2010). It is never a good idea for a depressed person to abruptly stop treatment.

            The common themes of these three patient’s experiences thus far is that they have not yet been pleased with their medications and that they all would or have benefited from therapy. John is experiencing serious side effects that might be identified early on if he was attending therapy. Jane has severe depression but studies show that antidepressants are more effective in severe cases and that cognitive behavioral therapy is a helpful treatment of depression on it’s own (Sipkoff 2012) (Med News Today 2005).  Jessie stopped taking her medication without the help of a doctor, a mistake that was immediately identified by her counselor and rectified. Patients are not experts on their treatment plans in the majority of cases. Antidepressants are serious medicines that affect the mood and mind of the people taking them and as such, the administration of these pills should be monitored regularly by at least one doctor of some expertise. Additionally in adolescents, therapy has been generally shown to increase the effectiveness of antidepressants and to make recurrence less likely after remission has been achieved (Johns Hopkins 2004).

            John’s shoplifting and other erratic behavior escalated. He and his wife are struggling in their marriage. He feels helped by the antidepressant but yet he becomes more suicidal by the day. John is arrested for attempting to steal a tire from a nearby super store. He did little to nothing to conceal his identity. John’s wife feels confused and betrayed by his recklessness and she leaves him. John’s behavior at his trial is similarly erratic, resulting in jail time. John has encountered one of the most serious possible outcomes of antidepressant treatment: mania and or increased suicidal tendencies. His life is perhaps irrevocably altered. People fighting against the use of antidepressants often use this type of story, of which there have been real occurrences. In Peter Breggin’s book, Medication Madness: A Psychiatrist Exposes Dangers of Mood Altering Medications, a series of stories illustrate the devastating effects of drug-induced mania. Mania is defined as “an abnormally elated mental state, typically characterized by feelings of euphoria, lack of inhibitions, racing thoughts, diminished need for sleep, talkativeness, risk taking, and irritability” (Free Dictionary 2012). The consequences of this side effect can be serious, however, the rarity makes it difficult to use it as an argument to stop the prescription of antidepressants altogether. With more attentive doctors, more cautious patients, and more counselor access, this side effect and the suicidal side effect can be detected early on and dealt with without lasting harm to the patient.

            John’s experience with antidepressants lasted two weeks due to severe side effects. Jessie has made a new appointment with her psychiatrist at this point. The psychiatrist decides to switch Jessie to bupropion (brand name Wellbutrin) due to Jessie’s discomfort on the previously prescribed SSRI. Bupropion is a NDRI, or norepinephrine and dopamine reuptake inhibitor and it is the only medication of this type approved for use in treating depression (E-Med 2012). One of the greatest advantages of this medication is that it has shown especially effective in children where many other antidepressants have fallen short (Glod 2004). Studies have shown that tricyclic antidepressants are completely ineffectual in children (Hazell 1995). SSRI antidepressants are minimally effective but can prove to help prevent recurrence of depression in children if administered along with psychotherapy (Tsapakis 2008) (Johns Hopkins 2004). Because Jessie is under the age of eighteen and therefore classified as a child, her depression treatment options are limited for reasons that are not completely clear. It is possible that the medicines affect the children differently due to their developing brains. It has been shown that children are more susceptible to the side effect of increased suicidal tendencies (NEJM 2004). This is a huge problem. Children desperately need effective depression treatments just as much as adults (Tsapakis 2008). One site claims "pre-schoolers are the fastest-growing market for antidepressants. At least four percent of preschoolers -- over a million -- are clinically depressed" (Uplift 2012). Now consider that for all of the grade levels and it becomes clear that children cannot afford to be immune to antidepressant treatment. Luckily, atypical medicines like bupropion are providing new hope in this demographic (Glod 2004).

            While Jessie has moved on to bupropion and has seen much success in combination with therapy over the last few weeks, Jane has been struggling through her nausea to give the antidepressant time to reach its full effects. However, after six weeks, she insists that she is not feeling either less depressed or less sick. Due to the severity of her depression, her doctor prescribes a tricyclic antidepressant, the first line of defense after a failed SSRI trial (Schimelpfening 2012). As aforementioned, tricyclic antidepressants are not the first choice of most doctors due to their higher toxicity and potential for drug interaction (Daily Mail 2012). One particularly dangerous tricyclic antidepressant drug interaction is with MAOI antidepressants (Gillman 2012). If Jane does not find success with her tricyclic medication and wishes to try an MAOI antidepressant to target different monoamines, she will have to first carefully follow her doctor’s instructions to wean off of her current medicine completely before introducing the new one. Luckily for Jane, her tricyclic antidepressant seems to work along with her continued therapy.

            Two of the hypothetical patients eventually found a helpful antidepressant. However, can this success be attributed to the antidepressant? The placebo effect is the concept that if a patient expects certain results from a medication, they will perceive those results (MedTerms 2004). In clinical trials comparing antidepressants with placebos, placebos have been known to achieve up to a 70 percent response rate (Lakoff 2012). Typically, antidepressants outperform placebos by approximately 15 percent in their response rates (Lakoff 2012). However, it has been shown that antidepressants are clinically superior to placebos, especially in severe cases (Sipkoff 2012). Therefore, it is safe to say that regardless of the amount of placebo effect potentially involved in a patient’s recovery, the decision to treat him or her with an antidepressant rather than a sugar pill is ideal. This study also looked into the concept of prescribing placebos to depressed patients under the guise of real medicine in order to induce a helpful placebo effect. The survey distributed on the ethics of this concept concluded that the majority of people think placebos belong in clinical trials and should not take the place of medication in real world doctor-patient interactions without the patient’s knowledge, regardless of whether a positive effect can be produced (Milam 2012a) (Milam 2012b).

            Thus far, this study has illustrated the value of integrative care, the superiority of antidepressants over placebos, and the need for effective depression treatment. Why is the effectiveness of an FDA approved type of drug under suspicion in the first place? The problem is that in America the main methods of confirming the value of a medication are believed to be FDA review and market success. If the FDA approves of it, it is considered by the general public to be safe for consumption. This is perhaps true to the extent that it is not rat poison, however, the FDA rarely performs it’s own studies to determine the quality of a drug  (FDA 2012). Instead, they rely on studies performed by the pharmaceutical company, a party with obvious interests in getting the drug on the market. The FDA primarily produces detailed warning labels (FDA 2012). One might think that the market would then come in to self regulate. If a medicine is dangerous, will that not become apparent after decades of use?

            The general public does not have a medical degree. They do not know much about the medicines they are prescribed. In medicine, there has historically been a great level of trust required to seek the attention of a doctor. It is more common now for patients to question their doctors but they may not always be asking the right questions. Antidepressants are a medicine that affects the mind. In this way, the positive and negative effects can be subtler than perhaps those of a surgical or other internal medicine treatment. The mind adds an unavoidable element of subjectivity to determining the efficacy of a drug. Depression is unavoidably unique to the individual. For that reason, this study concludes that the market does not know enough to reject ineffective mental health medicines on it’s own. The patient’s must seek awareness of their treatment, it’s risks and rewards and the doctor’s must seek an attentive understanding of their patient’s mental condition.
            Antidepressants are effective. They are more effective when combined with therapy for proper monitoring, support, routine, and other emotional coping tools. Any medication comes with its risk of side effects but side effects like mania or suicide produce a complex issue. These side effects are not irreversible, they are not permanent, but they can be just as damaging as heart valve failure if they go unnoticed. The difference is: with caution and knowledge on both the part of the doctor and the patient, antidepressants can be used in a way that will treat a serious mental condition that affects much of the population without producing lasting harm. Antidepressants are effective, but only if administered effectively.

           

           

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