Reprinted from the "Treatments: What Works?" issue of Visions Journal, 2015 15 (4), pp. 29-31
Antidepressants: Proper compliance is key
Depression is, in large part, a biological disorder. Changes occur in the brain of someone with depression. Imaging studies of the brain in depressed individuals show decreased brain activity, altered blood flow and disconnected circuits. These may be associated with changes in chemical messengers and other physiological functions.1
Early theories about depression suggested that symptoms were due to a lack of key chemical messengers in the brain: dopamine, norepinephrine and serotonin. Antidepressants work by increasing access to these chemical messengers, alleviating symptoms and enhancing brain activity.
All antidepressants have a similar response rate—it may take weeks for a patient to experience the full effect. But individual antidepressants differ in how they are used (i.e., form, frequency, scheduling), dosages given and possible side effects experienced. Some are activating and could be given in the morning, others are sedating so can be given in the evening, and some are sedating at low doses and activating at high doses, and vice versa.
Clinicians tailor treatment plans to an individual patient’s needs. It’s important to identify the right medication in the right dosage that will eliminate symptoms and produce few or no side effects. Some patients may require the addition of other medications to achieve a complete resolution of symptoms.
All antidepressants manage depression. Approximately two-thirds of individuals improve with initial antidepressant treatment.2
Unfortunately, patients don’t always take medications as prescribed. A lack of knowledge or a poor attitude about depression and antidepressants may result in patients not taking their medications as directed. This often results in poor response and negative outcomes. Studies indicate that older patients may have a more negative view of antidepressants.3,4 Reviews of patients taking antidepressants reveal a number of false beliefs:3,4
that antidepressants can change personality
that a person could take less medication on days when they feel better
that antidepressants are difficult to stop when taken for a long time
Effective antidepressants can have positive effects on indecision, memory, thinking and mood. They can also trigger medication-related effects such as activation, agitation, anxiety and restlessness. Individuals taking antidepressants should discuss all the effects they are experiencing—both symptoms and side effects—with their clinician.
Antidepressants work by stabilizing a brain system. It takes time for antidepressant medications to achieve the desired effect on mood. Taking less medication and/or ‘drug holidays’ will result in a drop in antidepressant levels, triggering a loss of response and resulting in a relapse. Abruptly stopping an antidepressant can result in rebound (re-emergence of symptoms that can be worse than the original symptoms) or withdrawal. Tapering off the antidepressant helps avoid withdrawal and allows the clinician to monitor for the re-emergence of mood symptoms.
Studies of adults and youth have identified that untreated depression is a reason that patients take their own life. Suicide is also more likely when individuals fail to take their medications. Most people who died by suicide hadn’t taken any antidepressants prior to death. Only 4% of people who take their own life intentionally overdose on antidepressant medications.5
Depression is a significant global health problem. Antidepressants can provide an effective treatment option for moderate to severe depression. But the most effective medication is the one the patient takes!
Clozapine: Benefits outweigh risks
Clozapine was developed in the 1960s. It was believed to be an antipsychotic less likely to cause the type of movement disorders associated with other medications. Clozapine was used worldwide until 1975.
In 1975, clozapine was withdrawn in Canada and the United States, though other countries continued to offer the medication. The withdrawal was due to reports of a serious side effect: agranulocytosis. Agranulocytosis describes a significant drop in a patient’s white blood cells. White blood cells fight infection, so a drop in levels puts the patient at risk of contracting infections. Only one to two patients out of 100 are at risk of developing agranulocytosis, and clozapine-induced agranulocytosis is reversed when the medication is discontinued.6
Clozapine was reintroduced in Canada and the US in l989 following studies that showed patients resistant to other antipsychotics may respond to clozapine.7 Mandatory lab monitoring of the blood cell count was introduced to identify those at risk of developing agranulocytosis.
Patients starting clozapine have lab work done weekly for the first 26 weeks. More frequent lab work may be requested if there’s a low count. Or, after six months, the frequency of lab work may be reduced to every two weeks, and after one year, to once a month. A decrease in the frequency of lab work reflects a decreased risk. After one year, the risk of developing agranulocytosis on clozapine is no greater than on any other antipsychotic agent.8
The longer psychosis is untreated, the greater the negative effects on patients. Individuals who fail to respond to two other antipsychotics should be considered for clozapine.9
Suicide is a major cause of death in patients with schizophrenia. Treatment with clozapine has been associated with a three-fold reduction in suicide for patients with schizophrenia.10 Clozapine takes time to work. One study reported that almost two-thirds of their patients had responded to clozapine by 12 months.11 Some clinicians have observed that patients continue to improve the longer they stay on this medication.
Timely and appropriate use of clozapine requires communication and collaboration between the patient, care givers and clinicians. But, despite the need for ongoing monitoring, clozapine benefits continue to outweigh the risks. Patients completing a self-assessment questionnaire reported achieving better “mental health” compared to other antipsychotic medications.12
Omega-3 fatty acids: What role do they play?
Omega-3 fatty acids—EPA (eicosapentaenoic acid) or DHA (docosahexaenoic acid)—are considered essential fatty acids. This means they are necessary for normal development and health. The brain contains large amounts of omega-3 fatty acids. Omega-3 fatty acids are integrated into cell membranes and help maintain the integrity and function of neurons (nerve cells). An inadequate intake of omega-3 fatty acids results in depletion of stores with negative effects throughout the body.
Humans cannot make omega-3 fatty acids, so they must be obtained from our diet. The best source is fatty fish (e.g., halibut, mackerel, salmon). Canola oil, flaxseed oil, leafy green vegetables and nuts are also sources of omega-3 fatty acids, but they provide limited quantities and require more energy to convert them to usable forms in our body.
Evidence suggests that omega-3 fatty acids have beneficial effects in schizophrenia and depression. There is also preliminary evidence suggesting benefit in bipolar disorder.
The largest body of literature investigating the impact of omega-3 fatty acids in psychiatric disorders focuses on schizophrenia. Decreased levels of omega-3 fatty acids have been observed in individuals experiencing their first episode of psychosis. People with schizophrenia can present with low levels of omega-3 fatty acids in cell membranes.13
Benefits of adjunctive use (i.e., alongside the primary medications) of omega-3 fatty acid in patients with schizophrenia or schizoaffective disorder may include:14
slowing the progression of psychosis in young patients
decreasing psychiatric symptoms
reducing the need for antipsychotic medications
increasing the efficacy of clozapine in patients with persistent symptoms
helping reduce medication side effects such as drug-related movement disorders
Inadequate stores of omega-3 fatty acids may also be a contributing factor for depression. Adding omega-3 fatty acids may help individuals on antidepressants who don’t achieve an adequate response to their medications.14
However, using omega-3 fatty acids to supplement traditional treatments used for psychiatric disorders has produced inconsistent results in studies. Reasons for some of the less promising results may include:13,14
the damage was already done by the time the illness was diagnosed
benefits from omega-3 fatty acids may take longer to occur than the studies allowed for
variations in the purity and consistency of omega-3 fatty acid products
There is also inconsistent information about the ideal dose. Suggested doses range from one to four grams per day of omega-3 fatty acids.
Still, omega-3 fatty acids do have psychiatric and medical (e.g., reduced cardiovascular disease, diabetes prevention) benefits, although these benefits may take time to occur. Omega-3 fatty acids are generally accepted and well tolerated by patients but should not be considered a replacement for traditional treatment options. Augmenting current treatment by the addition of over-the-counter herbal medications or supplements should always be discussed with the patient’s health care provider prior to use. This discussion should include the goals of the proposed augmentation, side effects and interactions.
Perfect medications do not exist. Identifying the most effective medication, or medications, takes time and takes into consideration the individual’s needs and response.
The risks and benefits of every medication should be discussed with the patient to address concerns. Once a medication is selected, patients should be monitored for efficacy and side effects.
If you have questions about your medications, your local pharmacist is available to help with your concerns.
About the author
Deborah is the Clinical Pharmacy Specialist for the Fraser Health Psychosis Treatment Optimization Program. She has worked with clinicians in community mental health centres and dedicated psychiatric facilities. Deborah also provides education about medications and mental illness through presentations, workshops and articles to consumers, staff and programs
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