Medications used for depression
When we talk about depression, the conversation normally doesn't go very far before the topic of medication is brought up. The following is from an in-depth report by the American Accreditation HealthCare Commission. If you have questions on anti-depressants, a phone call to your doctor or counselor can help you determine whether or not medication is right for you.
Drug Treatment Guidelines
MAJOR CLASSES OF ANTIDEPRESSANTS AND GENERAL TREATMENT GUIDELINES
Major classes of antidepressants include:
- Selective serotonin-reuptake inhibitors (SSRIs). These drugs have become the standard antidepressants. They target the brain chemical (neurotransmitter) serotonin. They can be effective and usually have moderate side effects.
- Other neurotransmitter inhibitors . These drugs target neurotransmitters other than or in addition to serotonin, such as norepinephrine. Many are proving to be effective in patients who do not respond to standard antidepressants or in specific patients, such as smokers who want to quit or patients with chronic pain.
- Tricyclic antidepressants (TCAs). These drugs are effective but can have severe adverse effects, particularly in older people.
- Monoamine oxidase inhibitors (MAOIs). These drugs include newer selective MAOIs. MAOIs are the most effective antidepressants for atypical depression, but have some severe side effects and require restrictive dietary rules and care to avoid drug interactions.
All of these drugs appear to work equally well, although they may vary in terms of side effects. Your doctor will select an antidepressant based on side effects, cost, and your personal preference.
Approach and Duration of Initial Treatment. The guidelines for the duration of an initial antidepressant regimen are generally:
- Patients should start at a low dose, which is increased over a period of 5 - 10 days.
- Patients should see their doctor every 1- 2 weeks until substantial improvement occurs. It may take 4 - 8 weeks before a patient experiences the effects of any antidepressant.
- Side effects usually diminish within 1 - 4 weeks. (Exceptions may be weight gain and sexual dysfunction.)
- If no improvement occurs within 6- 8 weeks of starting drug treatment, the doctor may either increase the dosage or switch to an alternative drug. More than 80% of patients respond to some antidepressant, although specific drugs are helpful for only about half of patients. This suggests that if one medication fails, another has a good chance of being helpful. In general, the fewer drug treatment strategies required, the better a patient's chances of recovering completely from depression. Patients who become symptom-free have the best chance for complete recovery compared to patients whose symptoms merely improve.
- In general, patients are asked to continue taking antidepressants for at least 4 - 9 months after symptom relief to help prevent relapse. Patients who have had at least 2 episodes of depression may need to continue drug treatment for longer than 9 months. (Patients who improve within 2 weeks of taking medications may not require lengthy treatment.)
Treating Recurrence. Recurrence of depression is very common. About a third of patients will relapse after a first episode within a year of ending treatment, and more than half will experience a recurring bout of depression at some point during their lives. Among those at highest risk for early relapse and who may require ongoing antidepressants are:
- Patients with at least two episodes of major depression or major depression that lasts for 2 years or longer before initial treatment.
- Patients who continue to have low-level depression for 7 months after starting antidepressant treatments.
- Patients may need maintenance therapy. Doctors disagree, however, on the optimal length or the appropriate dosage of maintenance therapy. Some patients may need to stay on antidepressants for 1 - 2 years -- or even indefinitely. Some doctors recommend withdrawing from medication after a year. (This should be done gradually, over 2 - 3 months.) If depression recurs, the patient should go back on the antidepressants.
There is no risk for addiction with current antidepressants, and many of the common antidepressants, including most standard SSRIs, have been proven safe when taken for a number of years.
Common Side Effects of Most Antidepressants. No matter how well a drug treats depression, the ability of patients to tolerate its side effects strongly influences their compliance with therapy. Lack of compliance is probably the major barrier to success. Side effects can be avoided or moderated if any regimen is started at low doses and built up over time. Although specific side effects are discussed under individual drugs, there are a few that are common to many of them:
- Sexual dysfunction is a common side effect of many of the standard antidepressants and some of the newer drugs. Some antidepressants, such as bupropion, do not pose as high a risk for this problem. Sildenafil (Viagra), used for erectile dysfunction in men, may help reverse sexual dysfunction from antidepressants. It does not heighten sexual interest, however.
- An increased risk of oral health problems caused by dry mouth is associated with long-term use of many antidepressants, particularly tricyclics. Patients can increase salivation by chewing gum, using saliva substitutes, and rinsing the mouth frequently.
- Virtually all antidepressants have complicated interactions with other drugs; some are very important. Patients should inform the doctor of any drugs they are taking, including over-the-counter medications and herbal remedies.
- Nearly all antidepressants are metabolized in the liver, so anyone with liver abnormalities should use them with caution.
- Abrupt withdrawal from many antidepressants can produce severe side effects; no antidepressant should be stopped abruptly without consultation with a doctor.
SUICIDE RISK AND ANTIDEPRESSANT MEDICATIONS
In recent years, there has been concern that SSRI antidepressants can increase the risk for suicidal behavior. Of particular concern is a greater risk for suicide in young people taking these medications. While depression is itself the major risk factor for suicide, and antidepressant medication may revitalize suicidal attempts in patients who were too despondent before treatment to make the effort, evidence suggests that in some cases the medication itself can cause suicidal thoughts and behavior (suicidality). Paroxetine (Paxil) appears to have the strongest association with increased suicidal risk, particularly in younger adults.
In the U.S., all antidepressant medications now carry “black box” warnings on their prescribing label explaining the association between antidepressant use and increased risk for suicidality in children, adolescents, and young adults ages 18 - 24, especially during the first few months of treatment. The FDA’s data do not show an increased risk for suicidality in adults older than age 24. Adults age 65 years and older taking antidepressants have a decreased risk for suicidality.
The FDA recommends that caregivers monitor children, adolescents, and young adults being treated with antidepressants for sudden behavioral changes, and immediately notify their doctor if such changes occur. These behavioral signs include:
- Panic attacks
- Hyperactivity in actions and speech
- Worsening of depression
- Increased thoughts of suicide
The FDA’s guidelines for medication usage also recommend that all patients see their doctors regularly after initiating drug treatment. The recommended schedule is:
- Once per week for 4 weeks (1st month)
- Every 2 weeks for the next month (2nd month)
- At the end of week 12 following the start of drug treatment (3rd month)
- More frequently if changes in mood or behavior occur
- Patients should also be closely monitored if their drug dosage is changed.
Patients should immediately contact their doctor if depression symptoms worsen or if suicidal thoughts or behavior increase.
SELECTIVE SEROTONIN-REUPTAKE INHIBITORS (SSRIS)
Selective serotonin-reuptake inhibitors (SSRIs) are now the first-line treatment for major depression. They work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro). There do not appear to be significant differences among SSRI brands in effectiveness for treating major depressive disorder, although individual drugs may have different side effects or benefits for specific patients.
At this time, fluoxetine and escitalopram are the only antidepressants approved for treatment of major depressive disorder in adolescents (ages 12 - 17). Fluoxetine is also approved for children age 8 and older. Because they act specifically on serotonin, SSRIs have fewer side effects than older antidepressants, which have more widespread effects in the body.
Candidates for SSRIs. SSRIs appear to best help people with the following conditions:
- Mild-to-moderately severe major depression
- Seasonal affective disorder
- Severe premenstrual syndrome and premenstrual dysphoric disorder (PMDD). A repackaged form of fluoxetine (Sarafem) is the first SSRI specifically FDA-approved for PMDD. Other SSRIs and newer antidepressants are also proving to be effective.
- Anxiety disorders
Duration of Effectiveness and Use. SSRIs take, on average, 2 - 4 weeks to be effective in most adults. They may take even longer, up to 12 weeks, in the elderly and in those with dysthymia. By 14 weeks, depression should be in remission in those who respond to the drugs. Unfortunately, recurrence is common once the drugs are stopped. Studies indicate that the standard SSRIs are generally safe to be taken long term, although it is still unclear which patients most benefit from on-going medication. Some doctors recommend withdrawing from medication after a year. If depression recurs, then the patient should go back on the antidepressant.
Side Effects of SSRIs. Side effects may include:
- Nausea and gastrointestinal (GI) symptoms usually wear off over time.
- Agitation, insomnia, mild tremor, and impulsivity occur in 10 - 20% of people who take SSRIs. These symptoms may be particularly problematic in patients who also suffer from anxiety, sleeplessness, or both.
- Drowsiness affects about 20% of SSRI-treated patients. Newer SSRIs, such as escitalopram (Lexapro), may have fewer of these adverse effects.
- Dry mouth is a common side effect.
- Patients may lack motivation, feel tired, be confused, and experience mental dullness, but this side effect is fairly rare.
- Headache and flu-like symptoms may occur.
- Heart palpitations and chest pain may occur.
- Weight gain varies depending on the SSRI. Patients should be encouraged to maintain a low-calorie diet and to exercise. They should be aware that some of the weight-loss medications, notably sibutramine (Meridia), can have serious interactions with SSRIs.
- Sexual side effects include delayed or loss of orgasm and low sexual drive. They are a well-known side effect of SSRIs. Taking a supervised drug "holiday" on the weekend may improve sexual function during that time. Some of the newer SSRIs or other antidepressants may cause less severe impairment of sexual function.
- Paroxetine (Paxil) may cause birth defects if taken during the first 3 months of pregnancy. Most reported defects have been heart-related. The most common heart abnormalities are ventricular septal defects, which are holes in the muscular wall that separate the main pumping chambers of the heart. Still, recent research suggests that most types of SSRI-associated birth defects are rare and the overall risks are low. Pregnant women who are being treated for major depression should not stop taking antidepressants without first talking to their doctors.
- SSRIs can worsen manic symptoms in patients with bipolar disorder.
Drug Interactions. SSRIs can interact with other antidepressants such as tricyclics and, in particular, monoamine oxidase inhibitors (MAOIs). Due to a potentially fatal condition called serotonin syndrome, SSRIs should never be taken in combination with an MAOI or within 2 weeks after discontinuing MAOI treatment.(For more on serotonin syndrome, see MAOI section below.) Other serious interactions can occur with meperidine (Demerol) and illegal substances (such as LSD, cocaine, or ecstasy). SSRIs also interact with the antibiotic linezolid (Zyvox). People who take SSRIs may drink alcohol in moderation, although the combination may compound any drowsiness experienced with SSRIs, and some SSRIs increase the effects of alcohol.
Withdrawal Symptoms. Cognitive problems, sleep disturbances, increase in depressive symptoms, and electric shock-like symptoms have been known to occur with sudden discontinuation of SSRIs. The symptoms are more likely to occur with antidepressants with shorter half-lives as compared with fluoxetine, which has a long half-life. The dose of the antidepressant should be slowly reduced before stopping.
OTHER NEUROTRANSMITTER INHIBITORS
These antidepressants target other neurotransmitters, such as norepinephrine or dopamine, alone or in addition to serotonin. In general, the advantages of these antidepressants are:
- They may be better tolerated than the older tricyclic compounds and even some SSRIs, although long-term side effects are not fully known in this group.
- Most of these drugs have fewer adverse effects than SSRIs on sexual function.
- They may be more effective than SSRIs for severely depressed patients.
- Some of these drugs may be helpful for additional problems -- such as insomnia, fibromyalgia and similar chronic pain syndromes, or smoking -- that affect some people with depression.
These drugs do share some side effects with other antidepressants, including dizziness and dry mouth.
Dual Inhibitors. Dual inhibitors act directly on two neurotransmitters -- norepinephrine and serotonin. These drugs are also known as serotonin norepinephrine reuptake inhibitors (SNRIs). The following SNRIs are approved for treatment of major depression in adults:
- Venlafaxine (Effexor)) is similar to Prozac in effectiveness and tolerability for most patients. Desvenlafaxine (Pristiq) is chemically related to venlafaxine. As with SSRIs, venlafaxine may impair sexual function. The drug can increase blood pressure and heart rate and should be used with caution in patients with high blood pressure or heart disease. It can also cause uterine and vaginal bleeding unrelated to menstruation. Venlafaxine should not be taken during the last trimester of pregnancy as it can cause complications in newborn infants. Some patients report severe withdrawal symptoms, including dizziness and nausea. Because of overdose risks, doctors should prescribe patients limited quantities of venlafaxine pills.
- Duloxetine (Cymbalta) also acts on both serotonin and norepinephrine. Side effects are generally mild and may include dry mouth, nausea, and sleepiness. Patients with narrow-angle glaucoma or patients with liver or kidney diseases should not take duloxetine. Because duloxetine can cause liver damage, patients who drink large quantities of alcoholic beverages should not take it. Signs of liver damage include itching, dark urine, yellowing of skin and eyes (jaundice), and fatigue. Patients should immediately contact their doctor if they experience these symptoms.
- Mirtazapine (Remeron) can cause sleepiness, increased appetite, weight gain, and dizziness.
Multiple Neurotransmitter Ihibitors (Bupropion). Bupropion (Wellbutrin, generic) affects the reuptake of serotonin, norepinephrine, and dopamine -- a third important neurotransmitter. In addition to depression, bupropion is also approved for treating seasonal affectiveness disorder (SAD) and, under the tradename Zyban, for smoking cessation. Bupropion causes less sexual dysfunction than SSRIs. About 25% of patients experience initial weight loss. Side effects include restlessness, agitation, sleeplessness, headache, and stomach problems. Bupropion has a risk for seizures, which increases with higher doses. High doses may also cause dangerous heart arrhythmias.
In 2009, the FDA warned that bupropion products may cause symptoms such as changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. Most of these symptoms were reported in patients who took bupropion to help stop smoking. However, the FDA also warns that patients who have major depressive disorder or other psychiatric illnesses (schizophrenia, bipolar disorder), may experience worsening of their symptoms while taking bupropion
Before the introduction of SSRIs, tricyclics were the standard treatment for depression.
Tricyclics are sometimes grouped into two categories:
- Tertiary amines include amitriptyline (Elavil, Endep) and imipramine (Tofranil).
- Secondary amines include desipramine (Norpramin) and nortriptyline (Pamelor, Aventyl). Secondary amines may have fewer side effects, including drowsiness, than tertiary amines, but they are as toxic in high amounts.
Less commonly used tricyclics include doxepin (Sinequan), amoxapine (Asendin), maprotiline (Ludiomill), protriptyline (Vivactil), trimipramine (Surmontil), mianserin (Bolvidon), and dothiepin (Prothiaden).
Tricyclics are as effective for treating depression but they have many side effects. They may offer benefits for many people with dysthymia, who generally do not respond to SSRIs. They may also be prescribed in lower dosages to be taken at night to help with insomnia.
Side Effects of Tricyclics. Side effects are common with these medications. In an analysis of studies, more tricyclic users discontinued their drugs due to side effects than did SSRI or MAOI users. Side effects most often reported include:
- Dry mouth
- Blurred vision
- Sexual dysfunction
- Weight gain
- Difficulty urinating
- Dizziness -- blood pressure may drop suddenly when sitting up or standing.
Tricyclics can have serious, although rare, side effects:
- They tend to cause disturbances in heart rhythm, which can pose a danger for some patients with certain heart diseases. Care should be taken when these medications are prescribed to the elderly and to those at risk of overdose. In particular, desipramine (Norpramin) has been associated with dangerous heart rhythm abnormalities in patients who have a family history of these problems.
- Also of concern are reports that tricyclics, particularly imipramine as well as mianserin and dothiepin, may increase the risk for a lung disease called idiopathic pulmonary fibrosis (IPF), which can cause lung inflammation and scarring. Initial symptoms are breathlessness and dry cough.
- Tricyclics can be fatal with an overdose.
- Protriptyline can cause sun sensitivity. People who take this drug should take precautions against sunlight when they go outdoors.
MONOAMINE OXIDASE INHIBITORS (MAOIS)
Monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, an enzyme which has negative effects on many of the neurotransmitters that are important for well-being. MAOIs include phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine (Parnate).
Newer MAOIs, such as selegiline (Eldepryl, Movergan), target only one form of the MAOI enzyme. They may cause fewer side effects than older MAOIs. A skin patch form of selegiline (Emsam) is also available for treatment of major depressive disorder in adults.
Candidates for MAOIs. Because these drugs can have very severe side effects, they are usually prescribed only for severe depression or when other types of antidepressants do not help (treatment-resistant depression). MAOIs may also be effective for the following conditions:
- Atypical depression
- Eating disorders
- Post-traumatic stress disorder
- Borderline personality
Side Effects. MAOIs commonly cause the following side effects:
- Orthostatic hypotension (a sudden drop in blood pressure upon standing)
- Drowsiness or insomnia
- Sexual dysfunction
- The most serious side effect is severe hypertension (high blood pressure), which can be brought on by eating certain foods having high tyramine content. Such foods include aged cheeses, most red wines, sauerkraut, vermouth, chicken livers, dried meats and fish, canned figs, fava beans, and concentrated yeast products.
- MAOIs can cause birth defects and should not be taken by pregnant women.
Serotonin Syndrome . Very dangerous side effects, such as serotonin syndrome, can occur from interactions with other antidepressants, including SSRIs. Serotonin syndrome is a potentially fatal condition that is caused by the interaction of serotonergic drugs. Symptoms include confusion, agitation, sweating and shivering, and muscle spasms. There should be at least a 2-week break between taking MAOIs and other antidepressants. MAOIs can have serious interactions with other drugs as well, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctors any other medications they are taking.
If patients fail to respond to antidepressants, doctors may try adding on a different type of drug. (This combination strategy is called “augmentation” or “adjunctive treatment”.) Atypical antipsychotics are drugs that are usually prescribed for schizophrenia or bipolar disorder, but they can also play a role in the treatment of severe depression. Two atypical antipsychotics, aripiprazole (Abilify) and quetiapine (Seroquel), are currently approved in combination with antidepressant therapy for treatment of adults with major depressive disorder.
Ketamine . Ketamine, an anesthetic drug, may be helpful for patients with severe treatment-resistant depression. In a small preliminary study, a single intravenous dose of ketamine helped patients quickly recover from depression within 2 hours, and some patients sustained benefits for up to a week. (Standard antidepressant drugs usually take about 8 weeks to have an effect.) Ketamine blocks the NMDA brain protein receptor, which is involved in glutamate regulation. Glutamate is a brain chemical that is thought to be involved in depression.