Depression is a prevalent and disabling disease. This course prepares health professionals to identify depression, educate, monitor and refer patients to appropriate healthcare services to assist patients in managing their depression.
Depression is a prevalent and disabling disease. This course prepares health professionals to identify depression, educate, monitor and refer patients to appropriate healthcare services to assist patients in managing their depression.
At the completion of this course, the learner will
Depression is a common problem in healthcare. Despite its prevalence, it is underdiagnosed and undertreated. This is unfortunate because there are many treatments available to provide relief to this disabling disease. Many reasons exist to explain why it is underdiagnosed, but most commonly it is not discussed enough in the medical office. Depression comes with a negative social stigma, and people are often ashamed to discuss it with their provider. In addition to doctors being reluctant to bring it up, they often lack time to dive into a discussion about depression with their patients.
Depression is more than feeling sad. Everyone has days when he or she is sad, but depression is a persistent feeling of sadness that disrupts life for the person afflicted and his or her loved ones.
This article will focus on major depressive disorder, but depression can have other forms. Major depressive disorder is associated with a reduction in pleasure and feelings of sadness that affects the individual’s ability to work, interact, eat, sleep and derive pleasure from life.
Another common type of depressive disorder is persistent depressive disorder, previously known as dysthymic disorder. This depression is associated with more than two years of symptoms that impair function, but symptoms are not as severe as in major depressive disorder.
Bipolar depression is another type of depression where the individual cycles between depression and mania. Mania is characterized by an elevated mood, increased energy, irritability and associated with euphoria, reduced sleep times, excessive talking and a lack of inhibitions.
Postpartum depression is associated with depression that occurs within 30 days of delivering a child.
Seasonal affective disorder is depression that starts in the fall and continues into the winter months and is associated with less natural light. This type of depression improves in the spring and summer.
Psychotic depression is a more complex form of depression and is associated with delusions and hallucinations.
Among adults in the United States, 6.7% of the population is depressed over a period of one year, and slightly more than sixty percent of these cases are considered to have severe depression. The prevalence of depression is higher in females than in males, 8.5 % vs. 4.8 % respectively.1
Depression is more common in those between the ages of 40 to 59 years old when compared to those over the age of 60 years old. Females are seventy percent more likely to be depressed than males over their lifetime. Non-Hispanic whites are much more likely to suffer depression than non-Hispanic blacks.1
Major depression is known to reoccur with a recurrence rate over a two year period of about 40 percent. When a patient has suffered two separate episodes of depression, three out of four will have another reoccurrence within five years.2
It is estimated annually that almost 60,000,000 people present to physician offices with a primary mental health diagnosis. Almost 4 percent of adults have been afflicted with serious psychological distress in the past month. Almost 40,000 deaths occur every year due to suicide – which is most often related to depression.3
Depression is laced with many complications. The most serious complication is suicide. Along with substance abuse, depression is the most common mental disease that afflicts those who commit suicide. The prevalence of suicide is not insignificant. It took the lives of 42,826 people in 2014.3
While depression is more common in women, successful suicide is more common in men. Women more commonly attempt suicide (2-3 times more often) but are not as successful. Older white men have the highest rate of completed suicide.4
Specific factors increase the risk of suicide, and these include: chronic medical illness, access to firearms, depression, family history of suicide, social isolation and delusions.4
Depression is associated with many other problems in addition to suicide. Those with depression suffer more medical illness and have worse outcomes in medical illness compared with those without depression. Depression significantly impacts work life. Those with depression are more likely to miss work and be inefficient at work. Depression can have a profound impact on quality of life. It significantly disrupts family, friend and work relationships. Some with depression are socially isolated and do not interact with other people. Severe cases of depression are associated with not leaving home.
Depression is associated with higher rates of substance abuse.It is unclear if depression causes substance abuse or if substance abuse causes depression. There is likely a complex interaction between the two conditions.
Depression may lead to significant complications on patient’s physical health. Depression may lower compliance with medical treatment. This may occur for many reasons including depression leading to patients making poor lifestyle choices or depression directly increasing the risk of disease.
Those with depression have reduced survival rates when compared to those without depression. Depression is a risk factor for heart disease and subsequent myocardial infarction.4In addition, those who have depression are more likely to have more severe cardiac symptoms, reduced quality of life and a worse prognosis in heart disease.5
Depression has also been noted to increase the risk of dementia. In a meta-analysis of patients without mild cognitive insufficiency or dementia at baseline, it was shown that those with baseline depression had a higher incidence of Alzheimer’s disease, vascular dementia, or mild cognitive impairment than those without depression.6
Those who are depressed are more likely to make poor lifestyle choices. Obesity rates are higher in those with depression than those without depression. A study confirmed that those who are obese are more likely to become depressed and those who are depressed are more likely to become obese. This finding was true for those over the age of 20, but not for those under 20 years old.7
The following case studies are descriptions of the patients presentation. The conclusion of the case study is presented later in this course after the discussion of treatment options.
Jenny, a 36-year-old married, white female with three children, presents to her primary nurse practitioner at her husband’s request because she has been increasingly irritable, tired all the time and complaining of dizziness and frequent low back pain. The physical exam was unremarkable.Routine blood work including a complete blood count, complete metabolic panel, and thyroid panel was unremarkable.
On follow up exam the nurse practitioner reviewed her labs and performed a Physician Depression Questionnaire (PDQ-9). The PDQ-9 score was 14 which equated with moderate depression. The patient denied any suicidal thoughts and no grief was noted. The exam did not reveal any manic or psychotic symptoms. The patient revealed that she had felt like this before, but the feelings did not persist and never impacted the lives of her family or friends.
John, a 78-year-old man, presents to his primary care physician with the complaint of low back pain. John lives with his son and daughter-in-law, and his son accompanies him to the appointment. The low back pain has been present for three weeks, and there has been no trauma or injury that would indicate a cause of the back pain. John reports that the pain is mild, but he is very worried that this is cancer. He is convinced that he is going to die.
John’s son is not as concerned about the low back pain; he reports that he has complained of on and off back pain his whole life. He is most concerned about his increased irritability and social withdrawal. John’s past medical history is positive for hypertension, arthritis and mild dementia. He has never had surgery.
He lives with his son because his son had noticed an increase in confusion after the death of his wife one year ago. He was not able to cook, clean or handle finances, but is still able to drive and shop. Over the past couple of months, he has become more isolated in his room and has had increased irritability. His daughter-in-law is threatening him to put him in a nursing home. He has limited contact with his friends after moving in with his son and has no friends in his new neighborhood. His son discourages him to drive the 20 miles to visit his old friends.
The physical exam was unremarkable. His mini-mental state exam was 19/30, and his Cornell depression score was 9.
The exact pathophysiology of depression is unknown, but there are many theories. It is likely caused by a combination of factors including biochemical factors, genetics, psychological factors and environmental factors. Major theories revolve around disturbances in neurotransmitters and chemicals in the central nervous system, particularly serotonin, norepinephrine and dopamine.
It is clear that depression runs in families, but exactly how it is transmitted is not known. It is likely that there are multiple genes interacting together that increase the risk of depression.8 Individuals with a family history of depression or alcohol dependence have a higher risk of depression.4
Life can contribute to depression. Stressors and interpersonal loss are often associated with depression. Trauma, loss of a loved one, a difficult relationship, or any stressful situation may trigger a depressive episode. Stress increases cortisol levels and may affect mood. An early life loss increases the risk of depression over a lifetime. Some depressive episodes occur in the absence of an obvious cause.
Depression presents differently in different individuals. A common pneumonic to help nurses remember the classical signs and symptoms of major depressive disorder is SIG-E-CAPS.
|S||Sleep disturbances either not sleeping enough (usually early morning wakening) or excessive sleep|
|I||Loss of interest in activities that the individual used to find enjoyable anhedonia|
|G||Guilt or feeling worthless or hopeless|
|E||Low energy and/or fatigue|
|A||Appetite disturbances either eating too much or too little|
|P||Psychomotor retardation or agitation|
|S||Suicidal thoughts or attempts|
Other symptoms that can present with depression include: irritability, restless, pessimism, a variety of pain complaints, headache or gastrointestinal problems.
According to the DSM-V criteria, to meet the diagnostic criteria for major depression an individual must have 5 signs/symptoms over a two week period that is a change from previous function. Depressed mood and/or reduced interest/pleasure must be present, in addition to at least 4 other criteria described above.
In addition, the individual must not have manic episodes. The symptoms must cause impairment in function or significant distress. Other medical problems (such as hyperthyroidism, drug abuse or alcohol abuse) must be ruled out, and the symptoms must not be related to bereavement/grief.
It is often more challenging to diagnose depression in those who have dementia. Those with dementia may demonstrate increased agitation, irritability, fatigue or an increase in hallucinations and/or delusions. Those with dementia may be less likely to have feelings of hopelessness/helplessness or guilt.
Children who are depressed have a higher risk of developing severe depression when they become adults.9 Children may present differently with depression when compared to adults. Children with depression may practice avoidance behaviors, including refusing to go to school, pretending to be sick or not wanting to leave the parent's side. They may also demonstrate behavioral problems, get into trouble, be irritable or have mood swings. Many of these behaviors are common among teenagers without depression, and it is often difficult to determine if depression is present in children.
Physical exam is typically unremarkable in the depressed patient. Certain features may be noticed on exam includingflat affect, poor personal hygiene, psychomotor agitation or retardation and/or slow speech. Many patients with depression will have none of these features. Mental status should be checked, particularly in the older patient, to tease out any cognitive decline. The exam should attempt to bring out any of the key features of depression noted above as well as any mood swings, delusions and hallucinations.
No test definitively diagnoses depression, but diagnostic testing is used to rule out other contributing or causative factors of a depressed mood. Common blood tests run in the depressed patient include:
Imaging studies are rarely performed in the management of depression. Some patients may be candidates for a computed tomography or magnetic resonance imaging for the brain to rule out intracranial pathology. Rarely electroencephalography (EEG) or lumbar puncture is performed.
Few patients discuss depression with their primary care provider (PCP). Many patients with depression present with somatic symptoms (commonly pain issues such as headache, myalgia or back pain), making diagnosis much more challenging.
Because few patients readily bring it up to their PCP, screening for depression is very important. Without screening only about 50 percent of patients with major depression are diagnosed.10Detecting depression is important because untreated depression increases the risk of suicide, reduces quality of life, contributes to poorly controlled chronic diseases and increased death rates.4The US Preventive Services Task Force (USPSTF) advocates regular screening for depression in adults if staff is available for diagnosis, treatment and follow up.11
Screening is essential as depression is a common condition that often goes undetected. Multiple tools are available to screen in primary care. Screening has been found to detect the condition, but it has not been proven to enhance clinical outcomes.11The downside to screening includes potential overdiagnosis of patients, unnecessary treatments, overtreatment with resultant unnecessary side effects and extra costs of treating a disease that is not present.
Screenings may be done by performing a screening test on all patients during routine visits which is recommended by the US Preventive Services Task Force. Screening may also occur in patients who present with certain finding suggestive of depression such as chronic pain, insomnia, unexplained symptoms, fatigue, life stressors, recent life changes or fair/poor self-health ratings.
A few of the common screening tests to evaluate for depression include:
A quick screen, the Patient Health Questionnaire-2 (PHQ-2), for depression can be run by asking the patient two questions. This test has a sensitivity of 83 percent and a specificity of 90 percent.4 A single yes response is a positive test.
Depression is a diagnosis of exclusion. No diagnostic test is available to diagnose the disease definitely. When it is suspected, other conditions must be ruled out. This is done with a history, physical exam, selected blood tests and occasionally radiographic tests to rule out conditions that may mimic depression.
In order for the condition to be managed appropriately, it needs to be diagnosed. A new clinical guideline recommends screening adults for depression when there is a place to ensure a correct diagnosis, appropriate treatment and follow up.12 A similar statement has been made for adolescents with depression. Those between the ages of 12-18 years-old should be screened for major depression if a system is in place to accurately diagnose, provide psychotherapy and follow up. For those between 7-11 years-old, there is not enough evidence to evaluate if screening is appropriate.13
Depression often co-exists with other mental health conditions. Healthcare professionals need to be on the lookout for other conditions. Identifying other conditions is important because it can significantly impact treatment options. For example, certain antidepressant medications are indicated for both anxiety and depression. Other antidepressant medications, while treating the depression, will make the anxiety worse.
One of the most common co-existent conditions is anxiety disorders. Anxiety disorders may include generalized anxiety disorders, social phobia, obsessive-compulsive disorder, panic disorder and post-traumatic stress disorder.
Other mental health conditions that may co-exist with depression include substance and alcohol abuse, personality disorders, bipolar disease, eating disorders, adjustment disorder and schizophrenia.
In addition to mental illness, depression often co-exists with many medical diseases. Depression may be the result of the medical disease or depression may exacerbate the medical disease. Common medical illnesses that are seen in combination with depression include heart disease, cancer, stroke, Parkinson's disease, dementia and diabetes.
When evaluating someone with depression, identifying these medical conditions is critical in relation to the medication selection. For example, individuals with high blood pressure and heart disease may want to avoid certain antidepressants that increase blood pressure such as venlafaxine.
Depression adversely affects chronic disease. Those with depression typically have more severe underlying medical illness and more cost associated with their medical illness.14 When faced with a person with probable depression it is important to consider other diagnoses. Some of them include:
Some medications can cause depression. Common medications to consider as causes of depression include Beta blockers, calcium channel blockers, corticosteroids, H2 blockers, sedatives, chemotherapy agents or hormones.
A variety of treatments are available to manage depression. Common treatments include lifestyle changes, psychotherapy, medications, electroconvulsive therapy and light therapy.
The goal of treatment is remission of symptoms and to restore the function of the patient. For mild to moderate unipolar depression, treatment with pharmacotherapy and psychotherapy is better than either therapy alone15, but either option alone is another alternative.16 Studies have shown that those who are treated with psychotherapy will have benefits that will persist and those treated with antidepressants are more likely to relapse.15
Exercise is helpful as a treatment and as an add on method in the treatment of depression. It has been shown that modest levels of exercise may improve depression. It is unclear how much and the exact type of exercise that is helpful in managing depression, but getting patients to adhere to an exercise regime is critically important in the management of depression.17
No scientific proof exists to suggest that nutrition will cure depression, but eating a healthy diet may improve some of the symptoms of depression. Depressed patients should be encouraged to eat a balanced diet that provides adequate vitamins and minerals. Research suggests the following links between nutrition and depression20:
Talk therapy can be used to treat depression either alone or in combination with medications. In a large meta-analysis, psychotherapy was determined to be more effective than placebo, and the total number of sessions was not associated with the degree of clinical benefit. For mild to moderate major depression, psychotherapy and medications are generally comparable.11
The two most popular therapies are cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). Cognitive behavioral therapy helps change thought patterns and behaviors to improve mood. It is believed that the way one thinks and behaves contributes to their depression. Interpersonal therapy helps people with relationships that may be contributing to their depression.
Talk therapy is more effective in certain groups of people. Talk therapy is recommended for those with mild to moderate depression. In severe depression, it is recommended to stabilize the patient on medications before implementing talk therapy. A combination of talk therapy and medications is ideal for adolescents with depression.18
Psychotherapy helps to address the causative factors and the maintaining factors in depression. It is most effective in moderate-to-severe depression after a medication has stabilized the disease.
For those individuals with mild depression, the use of self-guided, self-help therapy may be considered. This may involve the use of a structured workbook or guidance by a clinician. If this option is attempted, the patient should let the staff know if there is no response, any worsening or any suicidal ideation. Research suggests that there is a small, but significant benefit to this type of treatment.19
The use of relaxation techniques such as relaxation imagery, progressive muscle relaxation and autogenic training is better than no treatment but less effective than psychotherapy.20
Many medications are available for the treatment of depression. Medications used to manage depression work mainly by altering the chemicals in the brain, particularly serotonin, norepinephrine and dopamine. Medications take a period of time before they work. The effect may be noticed as early as one to two weeks, but it typically requires four to six weeks before a significant effect is noticed.
Medications for depression are not as effective as medications for many other conditions. An analysis showed that 38% of those treated with antidepressants did not have a positive response in 6-12 weeks.21
It is critical that those with depression are diligent and follow up with their healthcare provider to assure that medication management is optimized. The first drug at the initial dose is often not enough to provide an adequate response for depression. The dose often needs to be increased, or the medication needs to be changed or augmented. Follow-up is also critical because the FDA suggests that all agents that have antidepressant properties may increase the risk of suicide – especially in patients under the age of 25.
Many different medication choices are available for the management of depression. The medication choice depends on multiple factors including physician preference, patient preference, adverse side effects and co-morbid conditions.
For years the treatment of choice for depression was tricyclic antidepressants (TCAs). Common TCAs include desipramine (Norpramin), amitriptyline (Elavil), nortriptyline (Pamelor), doxepin (Sinequan) and imipramine (Tofranil).
With the advent of newer antidepressants (selective serotonin reuptake inhibitors and others), the TCAs have fallen out of favor. TCAs have more side effects when compared to the newer agents. Selective serotonin reuptake inhibitors (SSRIs) have many advantages over TCAs. Common side effects of TCAs include urinary retention, drowsiness, blurred vision, dry mouth, constipation, orthostatic hypotension, lower seizure threshold and sexual side effects. One major concern with TCAs is that they are more lethal in overdose when compared to newer antidepressants. TCAs in high dose increase the risk of cardiac arrhythmia. They should be avoided after a heart attack or in those with ventricular arrhythmias or ischemic heart disease. TCAs are also associated with a number of drug-to-drug interactions. TCAs should not be used in those with narrow-angle glaucoma.
Monoamine oxidase inhibitors (MAOIs) are another older class of antidepressants. They are not used often today because of better-tolerated agents. MAOIs have the potential for serious interactions with both food and other medications, including over the counter medications. MAOIs are typically only prescribed by a prescriber who is well versed in monitoring these medications.
Individuals who take MAOIs and consume foods that contain tyramine have a significant risk of having a hypertensive crisis. Foods that are high in tyramine include yogurt, fava beans, aged cheese, soy sauce, avocados, meat tenderizer, raisins, pickled/cured fish or meat, sauerkraut and caviar. Alcohol should not be used in those on MAOI. All individuals who take these drugs need to be well versed in which foods they need to avoid and which medications that need to be avoided. Common side effects include sexual dysfunction, insomnia, orthostatic hypotension, anxiety and weight gain. Two common MAOIs are phenelzine (Nardil) and tranylcypromine (Parnate).
In more recent years serotonin reuptake inhibitors (SSRIs) have come on the market and have become a drug of choice for first-line treatment of depression. Medications in this class include fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa) and escitalopram (Lexapro). In comparison to older antidepressants, SSRIs are easy to titrate, have fewer side effects, have fewer drug interactions and are less toxic.
Different medications in the SSRI class have different side effects and different interactions, but a few common adverse effects include nausea, agitation, weight changes, delayed ejaculation, fatigue, impotence and restlessness. One major concern with SSRIs is that there are reports of increased suicidal thoughts and attempts in children on SSRIs with depression.
Fluoxetine (Prozac) is dosed at 20 mg in the morning and may be increased up to 80 mg a day. Each titration must occur after a few weeks on the medication. It is not indicated for those less than 8 years old. Fluoxetine has a long half-life and is the less likely to lead to withdrawal symptoms if abruptly discontinued. A weekly formulation is available that is dosed 90 mg once a week.
Fluoxetine can increase the levels of warfarin, phenytoin, carbamazepine, TCAs and benzodiazepines. It may lower the therapeutic effect of codeine. It may cause the serotonin syndrome when combined with other SSRIs and other antidepressants. It is pregnancy category C. Pregnancy category C means that there are no adequate animal or human studies that there are adverse fetal effects in animal studies but no human study data available.
Sertraline (Zoloft) is started at 25-50 mg orally every day, and the dose can be increased gradually to a maximum 200 mg per day. It is not indicated for those less than 6 years old. Common side effects include dizziness, fatigue, headache, insomnia, somnolence, diarrhea, nausea, tremor and diaphoresis. It may interact with warfarin, cimetidine, digoxin and diazepam. It is indicated for major depressive disorder, premenstrual dysphoric disorder, panic disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and social anxiety disorder.
Paroxetine (Paxil) has a short half-life and may lead to discontinuation syndrome when the medication is stopped, or doses are missed. It has the strongest anticholinergic effects of any of the SSRIs. For major depression, the standard form is dosed 10 mg per day to start to a maximum of 50 mg orally per day, and the extended-release form (Paxil CR) is dosed at 12.5 mg once a day to a maximum of 62.5 mg orally every day. Paroxetine is indicated for major depressive disorder, panic disorder, OCD, social anxiety disorder, generalized anxiety disorder, PTSD, and premenstrual dysphoric disorder. Side effects include somnolence, insomnia, dizziness, headache, nausea, xerostomia, constipation, diarrhea, weakness, tremor and diaphoresis. Sexual dysfunction is most problematic with paroxetine among the SSRIs.11
Fluvoxamine (Luvox) is approved for obsessive-compulsive disorders but is frequently used off-label in the treatment of depression and anxiety. The starting dose for adults is usually 50 mg once a day and has multiple drug interactions including benzodiazepines.
Citalopram (Celexa) is indicated for depression and is dosed at 20 mg once a day and the dose can be increased to 40 mg once a day after one week. It interacts with macrolide antibiotics, cimetidine, azole antifungal, omeprazole and carbamazepine. Side effects include: sleep disturbance, xerostomia, nausea and diaphoresis.
Escitalopram (Lexapro) is dosed at 10 mg once a day and may be increased to 20 mg after one week. It has few interactions but may interact with other SSRIs, cimetidine and alcohol. It is pregnancy category C. The FDA warns that both citalopram (more than 40 mg/day) and escitalopram (more than 20 mg/day) have the potential to prolong the QT interval, and may be fatal. They should be used cautiously in those with underlying heart disease and those who are prone to becoming hypokalemic.
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a newer class of medications to treat depression. Drugs in this class include venlafaxine (Effexor), duloxetine (Cymbalta) and desvenlafaxine (Pristiq), milnacipran (Savella), and levomilnacipran (Fetzima) . This class has a similar safety to SSRIs, but occasionally they may be associated with an increase in blood pressure. They can be used as a first line agent to treat depression or in those who do not respond to SSRIs. The SNRIs work on multiple neurotransmitters and do a better job at reducing the pain and other somatic complaints in depression when compared to other antidepressants.22
Venlafaxine (Effexor) comes as an immediate release form and an extended release form. The extended-release form is dosed 37.5 to 75 mg a day and may be titrated up to 225 mg a day. The immediate release form is started at 75 mg divided two to three times a day and titrated up to a maximum of 375 mg a day. It may interact with other antidepressants, cimetidine, diuretics and alcohol. It should not be used in those with severe uncontrolled hypertension. It is pregnancy category C. At doses less than 150 mg a day it mainly affects serotonin levels, but at higher doses is effects dopamine and norepinephrine levels. Discontinuation syndrome is high with this medication.
Desvenlafaxine (Pristiq) is dosed 50 mg once a day for adults. It may be titrated up to 400 mg once a day, but positive effects are not proven with higher doses (as reported by the manufacturer). Common side effects include nausea, headache, dizziness, dry mouth, insomnia, fatigue and bowel disturbance. It may interact with other SSRIs or blood thinners. It is pregnancy category C.
Milnacipran (Savella) is dosed 12.5 mg once a day on the first day and is titrated upwards to a maximum of 200 mg a day divided every 12 hours. It should be used cautiously in those with moderate to severe renal impairment and severe hepatic impairment. Those who take it may suffer from nausea, headache, dizziness, sleep disturbance and constipation.
Levomilnacipran (Fetzima) is started at 20 mg once a day and increased to 40 mg once a day. The maximum dose is 120 mg a day. Doses should be reduced in those with moderate and severe renal insufficiency. Common side effects include nausea but may also be associated with sexual dysfunction, constipation, urinary hesitancy, and elevated heart rate.
Duloxetine (Cymbalta) is dosed 20 mg twice a day to start and may be increased to 30 mg twice a day or 60 mg once a day in the adult. The maximum dose is 120 mg a day. It may interact with ciprofloxacin, SSRIs, TCAs, antiarrhythmic agents and anticoagulants. Common adverse effects include nausea, headache, dry mouth, dizziness, sleep disturbance and fatigue.
Duloxetine has multiple indications. It is approved for the treatment of depression in addition to diabetic peripheral neuropathy, chronic musculoskeletal pain, fibromyalgia and generalized anxiety disorder. This drug is often used by those who have depression in addition to one of these co-morbid conditions.
Other antidepressants include bupropion (Wellbutrin), mirtazapine (Remeron), vortioxetine (Brintellix), vilazodone (Viibryd) and trazodone (Desyrel). Generally, this group has low toxicity in overdose and may have an advantage over the SSRIs by causing less sexual dysfunction and gastrointestinal distress.
Bupropion is indicated for major depression, seasonal affective disorder and smoking cessation. It is indicated for those over 17 years old. It comes in many brand names including Wellbutrin XL, Wellbutrin SR and Aplenzin, and Forfivo XL. It increases the risk of seizure at higher doses, particularly in those with a history of seizures. Common side effects include headache, nausea, dry mouth, weight loss, dizziness and insomnia.
Mirtazapine (Remeron) is dosed 15 mg at bedtime and may be increased every 1-2 weeks up to 45 mg a day in adults. It is given at bedtime because one of its major side effects is sedation. Another common side effect is weight gain. Other side effects include dry mouth, constipation and dizziness.
Vortioxetine (Brintellix) was approved on September 30, 2013. The starting dose is 10 mg once a day and may be increased to 20 mg a day. The dose may be lowered to 5 mg a day in those who do not tolerate the higher dose. It works on multiple receptors and leads to increases in noradrenaline, dopamine and glutamatergic transmission. The half-life of the medication is long at approximately 57 hours leading to a low rate of withdrawal effects. Major interactions include linezolid, other antidepressants, fentanyl, ritonavir, tramadol and clopidogrel. Nausea is the most common side effect, but other side effects include diarrhea, constipation, dry mouth, headache and dizziness.
A recent review showed that vortioxetine was effective in the management of acute depression, but no more than SNRIs in general and less effective than duloxetine. The side effect profile is better with vortioxetine when compared to duloxetine. More research is needed to compare this agent to SSRIs.23
Vilazodone (Viibryd) selectively inhibits serotonin reuptake and does not work on dopamine or norepinephrine reuptake. It is dosed at 10 mg once a day for 7 days then may be titrated up to 20 mg then 40 mg once a day. This medication should be taken with food. It is commonly associated with diarrhea and nausea, and other side effects may include dizziness, dry mouth, insomnia and fatigue. Vilazodone (Viibryd) showed favorable effects on weight gain and possible less sexual dysfunction than other SSRIs.24
Trazodone is indicated for those 18 years of age and older. It is not commonly used as an antidepressant because it is very sedating.
Initial treatment for depression is typically done with SSRIs, but consideration may be given to a serotonin-norepinephrine reuptake inhibitor, an atypical antidepressant (e.g., bupropion, mirtazapine) or a serotonin modulator (e.g., vilazodone, trazodone). Tricyclic antidepressants and monoamine oxidase inhibitors are not recommended for initial treatment.
One large meta-analysis showed that sertraline and escitalopram are recommended as first-line agents due to their efficiency and acceptability. This same analysis showed that sertraline, escitalopram, mirtazapine and venlafaxine had a better response when compared to paroxetine, fluoxetine, duloxetine and fluvoxamine. Patients on sertraline, escitalopram or citalopram were least likely to discontinue therapy.25 Mirtazapine has a relatively rapid onset of action and a good side effect profile. In addition to treating depression, it has the potential to manage other symptoms including insomnia and weight loss.26
Research has not clearly defined a superior antidepressant, so the agent selected is dependent on multiple factors including drug-to-drug interactions, comorbid conditions, safety, side effects, cost, personal response or response of family members to medications in the past. Sometimes specific medications are helpful based on other symptoms or co-morbidities suffered by the patient. For example, those with insomnia may be prescribed trazodone or mirtazapine because of their sedating properties. Those who wish to stop smoking along with their depression may be considered to use bupropion. Escitalopram and citalopram are least likely to lead to drug-to-drug interactions and may be used in those on multiple medications.
Treatment is typically started at a low dose and slowly titrated upwards to the therapeutic range. Some response is typically seen within one to two weeks.27 Those individuals that respond early to treatment with antidepressants are more likely to go into remission.28 Up to three months of treatment is generally recommended to determine if the treatment was effective. In those who have minimal effect after 4-6 weeks, the treatment regime should be reevaluated.29
Medications need to be continued for at least 6-12 months for them to have lasting effects. If treatment is discontinued early, then there is a high risk of relapse. Most antidepressants need to be weaned gradually. Abrupt discontinuation of antidepressants can result in serious side effects known as the discontinuation syndrome. Medications should be discontinued over about 2 months for those on treatment for 6-12 months and up to 6 months for those on long-term treatment. Gradually tapering the medication is more critical if the patient is on a high dose.
A review of 37 studies showed that the antidepressants (fluoxetine or venlafaxine) were more effective than placebo in managing depression. The antidepressants effectively treated depression in 43% of cases, and the placebo was effective in 29% of cases. While antidepressants are effective, they are not as effective as many may believe.30 One study showed that on a scale from 0-52, antidepressants lead to a 2 to 4 point improvement when compared to placebo.31 Receiving a placebo is not equal to not receiving treatment. In clinical trials, the “placebo” group gets support in the form of regular meetings with health care providers and researchers.
Resistant depression is when treatment does not fully improve the condition. In resistant depression, standard treatments usually do not help. Sixty-seven percent of people fail to respond to first-line therapy.32 It is often not a failure of the medication, but a failure in the use of the medication. Failure can stem from the patient not taking the medication appropriately, the dose being incorrect, the patient not tolerating the medication or not using the medication for the correct amount of time.
When faced with treatment-resistant depression a few steps need to be taken. First, the clinician must reevaluate the diagnosis to assure that it is correct. Determine if there is a co-morbid factor that is contributing to the depression. Is there any anxiety, substance abuse or psychosis? Review the differential diagnosis list and determine if depression is still the diagnosis. Next, determine if the medication is being used correctly. Has an adequate trial been used, has the duration been long enough, has the patient taken the medication as prescribed?
If all of this checks out to be OK, a few strategies can be implemented.
For those with resistant depression, many medications are available to add to typical antidepressants to see if a response can be elicited. This can be particularly helpful if there is a co-morbid condition that is responsive to a specific medication. For example, those with psychotic depression may respond to an antipsychotic added to their antidepressant.
A meta-analysis found that adding an atypical antipsychotic is more effective than a placebo. This meta-analysis also showed that side effects are significantly more pronounced with antipsychotics.33 Common antipsychotics used in augmentation for depression include aripiprazole and olanzapine. Other augmentation strategies include: combining an SSRI and TCA; or adding triiodothyronine, buspirone, lithium, methylphenidate (Ritalin) or dextroamphetamine (Dexedrine) to an antidepressant.
St. John’s wort is an herbal remedy for the treatment of depression and has been around for many years. St. John's wort (Hypericum perforatum) is used as a primary agent for depression in Europe, but in the United States, it is an over-the-counter product. Its dosing is inconvenient as it is dosed 300 mg, three times a day. It is associated with nausea and should be taken with food.
Research suggests that it is no more effective than placebo in the treatment of moderate to severe depression. Some evidence suggests that it is helpful in mild to moderate depression.34 Ongoing research is looking at its benefits in other mood disorders.
Concern exists with some drug to drug interactions associated with St. John’s wort. Case reports have suggested that it may lower cyclosporine levels and could lead to organ rejection (in organ transplant patients). It may also interact with other SSRIs and may lead to serotonin syndrome. Serotonin syndrome most often occurs when two drugs that affect the body's level of serotonin are taken together. Other drugs that may lead to serotonin syndrome include many antidepressants, tramadol, migraine treatments such as the triptans, dextromethorphan or lithium. Symptoms occur within minutes to hours, and may include:
Other drugs that it may interact with St. John's wort include birth control pills, digoxin, warfarin and indinavir. Side effects include fatigue, dry mouth, headache, anxiety, dizziness, nausea and sexual dysfunction.
Electroconvulsive therapy (ECT) can be used in specific cases of resistant or severe depression. This type of therapy involves sending an electrical impulse to an unconscious patient which triggers a small seizure. It is done a few times a week for 2-4 weeks. Benefits may be noticed after a few treatments, but a full course is needed for maximal effectiveness. The patient is at high risk for relapse if there is no follow up.
ECT is believed to alter the chemistry of the brain. The benefits of this treatment are that it provides rapid onset of effect as opposed to other methods of treatments. It can be used in those with severe depression who are at high risk to commit suicide, those with catatonia, severe weight loss or those who are not eating. It is useful in those with depression and delusions and bipolar disease.4
ECT is associated with side effects. Confusion may occur, but this typically subsides within a few hours. No major long-term side effects are noted. Memory loss may occur. Most commonly it is retrograde amnesia which means that the patient may not recall things from just before the treatment. Retrograde amnesia typically improves after 1-2 months. Other side effects include headache and muscle aches. ECT is done under anesthesia which is associated with risk. The patient needs to be evaluated prior to the treatment to assure anesthesia is safe.
While no absolute contraindications exist to ECT, those with unstable cardiovascular disease, increased intracranial pressure or aneurysms are more likely to have complications.
Light therapy is primarily used in those with seasonal affective disorder. It involves being exposed to a bright light and is thought to change the circadian rhythm. This bright light gives off an intensity that is more than the typical lighting found in the home. This may affect brain chemistry to help reduce depression related to seasonal affective disorder. It can also be used in those with typical depression as an augmentation method to an antidepressant. Side effects are typically mild and usually only transient. Side effects include nausea, vomiting, fatigue, headache, agitation and sleep problems.
Light therapy should be used cautiously in those who have bipolar depression as it may precipitate a manic episode. In addition, those with sensitive skin or taking a medication (retinoids or some antibiotics) that increase sun sensitivity may want to avoid this type of therapy. Light therapy may not be effective as a solo therapy. It is often combined with other treatments for maximal effectiveness. Light therapy may take a few weeks to work, but some notice benefits in a few days.
Pregnancy and depression is a hot medical topic. It is a prevalent problem, but the use of medication has some potential drawbacks. It is particularly problematic because many people are on antidepressants when they get pregnant and abrupt withdrawal of these agents is problematic.
The American Psychiatric Association and the American College of Obstetricians and Gynecologists developed a statement to discuss how depression during pregnancy should be managed.35 The groups determined that depression increases the risk of preterm birth, miscarriage, fetal growth problems and developmental delay. Antidepressant medications were also problematic. Antidepressants increase the risk of low birth weight, miscarriage and pulmonary hypertension. Each case must be evaluated individually. Ideally, depression should be identified and treated before the female becomes pregnant. Individuals who become mildly to moderately depressed during pregnancy should participate in psychotherapy. Those with severe depression are the most problematic. A few options are available.
One glaring omission from the statement was the fact there was no recommendation about which medication to use during pregnancy if one is needed. There was a warning against paroxetine as this drug was associated with a higher risk of cardiac malformations. Although, this may be a class effect from the SSRIs. Infants born to mothers who took SSRIs after the 20th week of pregnancy had a six times higher risk of persistent pulmonary hypertension (PPHN) when compared to infants born to pregnant women who did not take antidepressants.
Other resources recommend the use of sertraline, citalopram or escitalopram for use in pregnancy as research suggests that these medications are associated with minimal risk of teratogenicity.36
Postpartum depression is also a major issue. It is very common with over 80% of women having a mood disturbance after childbirth.4 Most cases are mild, but it can be severe and lead to significant morbidity for the mother. The majority of antidepressants are safe for the breastfeeding mother, but there is not enough research to say this definitely. Like in pregnancy, psychotherapy is a safe option.
Infants born to mothers on SSRIs may exhibit a withdrawal syndrome as evidence by feeding problems, crying, increased muscle tone and shivering.
Bipolar depression is a mental health condition where there is both depression and manic episodes. Undiagnosed bipolar depression can be a common cause of resistant depression. It is critical that providers consider this when faced with resistant depression. Bipolar depression can be picked up if the clinician performs the Mood Disorders Questionnaire. Treatment of bipolar depression often requires the addition or the sole use of a mood-stabilizing agent such as lithium, divalproex sodium, olanzapine or quetiapine.
A black box warning has been posted on the use of some antidepressants indicating that antidepressant medications increase the risk of suicidal thoughts and attempts. This warning includes everyone taking antidepressants under the age of 25. There is a higher rate of suicidal thought and suicidal attempts in adolescents taking antidepressants than those taking a placebo.37
Clinicians need to closely monitor young patients on antidepressants especially in the early phase of treatment with antidepressants. Healthcare providers need to watch out for suicidal thoughts, depression that is becoming worse or behavioral changes such as withdrawal and agitation.
The majority of cases of depression are managed in primary care. Some situations require the management of a psychiatrist. Primary care doctors and the psychiatrist should work together to assure there is adequate treatment of the patient, especially those that are medically complex. The psychiatrist should be consulted when there is:
A psychologist is a helpful part of the team to help maximize depression therapy. Consultation with a psychologist is helpful when:
Jenny was given the diagnosis of depression and was started on Sertraline (Zoloft) 25 mg, and then the dose was titrated up after 2 weeks to 50 mg. She has a follow-up appointment in six weeks after the initial appointment. She reported that she had more energy, but was still feeling a little sad. Her dose was increased to 100 mg once a day. She was encouraged to see a psychotherapist, but she did not have time. At this point, her PDQ-9 score improved to 10; which while improved, still equated to moderate depression.
She had another appointment in 6 weeks. At this time she noticed an improvement in her mood but did not feel 100%. Her PDQ-9 score was 9, which is classified as the upper range of minimal symptoms. She reported having no side effects from the drug, so at this point, the nurse practitioner increased the dose to 150 mg. Even though her symptoms were classified as mild, she still had depression and given the improvement in response with the progressively increased dose and the lack of side effects the decision to increase the dose was carried out. At the follow-up appointment in 6 weeks, she reported that she had started seeing the psychotherapist that the nurse practitioner recommended and she felt as well as she had in years.
The point of this case study is that sometimes the dose needs to be pushed to achieve an adequate response. When medications improve mood, patients will at times consider getting themselves involved in therapy to enhance treatment.
John did not report depression on exam, but his irritability, social withdrawal and preoccupation with death were suggestive of depression. Depression is common after the loss of many social contacts. Dementia can cloud the depression picture. John reported that he is frustrated with his memory loss which was likely a contributing factor to his depression.
The patient was placed on escitalopram 10 mg and had a follow-up appointment in four weeks. This drug is a nice choice in the older adult because it lacks many drug interactions and has a rapid onset of action. At the follow-up appointment, the son reported that he was much less irritable, but continued with social isolation. The mini-mental state exam improved to 22/30 and his Cornell Depression Score increased to 10. At this point, the escitalopram was increased to 20 mg. The son was given the number of the local Alzheimer’s Association to help with support. The patient was also given the number of a psychologist to discuss some of his issues.
After another 4 weeks, the patient was feeling much better. He was involved with a therapist and in a social group of older adults. At his follow-up appointment, depression was not clinically evident.
Depression is a prevalent, disabling disease. Nurses need to take time to evaluate for depression using some of the many screening tools. In addition, the nurse needs to understand treatment options, so they are able to discuss them with patients. A major role of the nurse is to encourage patients to discuss depression with their primary healthcare provider.