Antidepressants

What are antidepressants and why are they involved in lupus treatment?

Anti-depressant medications are used to treat clinical depression or pain. Depression and anxiety are present in almost half of all people who have lupus and can be caused by the disease itself, by medications used to treat the disease, or by inadequate coping mechanisms. Clinical depression is different than the passing pangs of sadness that can haunt all of us from time to time. Rather, clinical depression is a prolonged, unpleasant, and disabling condition. The hallmark characteristics of depression are feelings of helplessness, hopelessness, general sadness, and a loss of interest in daily activities. Depression also often involves crying spells, changes in appetite, nonrestful sleep, loss of self-esteem, inability to concentrate, decreased interest in the outside world, memory problems, and indecision. In addition, people who are depressed may suffer from certain physiologic signs, such as headache, palpitations, loss of sexual drive, indigestion, and cramping. Patients are considered to be clinically depressed when they experience symptoms that last for several weeks and are enough to disrupt their daily lives. Lupus patients suffering from depression also often experience a general slowing and clouding of mental functions, such as memory, concentration, and problem-solving abilities; this phenomenon is sometimes described as a “fog.”

Some people think that people with chronic illnesses like lupus feel sad or depressed because they are sick. This notion can cause physicians and loved ones to dismiss or overlook clinical depression in people with lupus. While clinical depression can be caused by the emotional drain of coping with a chronic medical condition and the sacrifices and adjustments that are required of the disease, it can also be induced by steroid medications (e.g., prednisone), lupus involvement of certain organs such as the brain, heart, and kidneys, and other physiological factors. It is important that you speak with your doctor if you feel you are experiencing clinical depression, because many people who are physically ill respond well to anti-depressant medications. In addition, your doctor may treat your depression in different ways depending on the cause.

How do antidepressants work?

Most antidepressants work by slowing the removal of certain chemicals—neurotransmitters—from the brain. Neurotransmitters are chemicals that carry messages between neurons (nerve cells in the brain) and are important in the normal functioning of your brain. However, an imbalance in the amount of a certain neurotransmitter can cause a slowing of communication between neurons, and your normal feelings, emotions, or thoughts may become impaired. Antidepressants help people by making certain neurotransmitters associated with depression (specifically, dopamine, norepinephrine/noradrenaline, and/or serotonin) more available to the brain. The availability of more of a certain neurotransmitter means that more of this chemical will reach is target neuron, increasing communication and connectivity (neurotransmission) between the nerve cells in your brain and thus reducing certain symptoms of depression.

What kinds of medications are categorized as antidepressants?

Anti-depressant medications include four main kinds of drugs—tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), selective serotonin and norepinephrine reuptake inhibitors (SNRIs), and lithium. Other types of medications are also used, including venlafaxine (Effexor), bupropion (Wellbutrin, Zyban), mirtazapine (Remeron), and trazodone (Desyrel). Anti-anxiety medications and/or hypnotics (for insomnia) may be recommended in addition to antidepressants to help combat certain symptoms, and several combination therapies are also available.

How well do antidepressants work?

Six out of 10 people will feel better with the first antidepressant they try; however, the other 4 people will need to try another antidepressant until they find the one that is right for them. In addition, most people will need to take an antidepressant regularly for at least 6 weeks until they feel the full effect. You may also need to keep taking them for longer periods of time, even for the rest of your life.

What should I keep in mind while taking antidepressants?

Antidepressants can cause side effects that may mimic or intensify certain lupus symptoms. For example, antidepressants may cause an increase in the drying of mucous membranes, which could further aggravate symptoms in people with Sjogren’s syndrome (dry eye/dry mouth syndrome). In addition, antidepressants have been associated in rare cases among the general population (both non-lupus and lupus patients) with worsening of feelings of depression and suicidal thoughts. This side effect is especially prevalent early in treatment, during an alteration of dosage, or in people under 25. If you feel you are experiencing this effect, contact your doctor. You may need to stop the medication if symptoms worsen. However, you should not stop taking your medication without first speaking with your doctor. While most antidepressants are considered to be nonaddictive, suddenly stopping your treatment or missing doses can cause feelings of withdrawal, a phenomenon called discontinuation syndrome. Symptoms of this condition include nausea, headache, dizziness, lethargy, and flu-like symptoms. If you feel you should stop taking antidepressants, work with your doctor to slowly decrease your dose before you stop.

Types of Antidepressants

Tricyclic antidepressants (TCAs)

Amitriptyline (Elavil, Endep)
Amoxapine (Asendin, Defanyl, Demolox, Moxadil)
Clomipramine (Anafranil)
Desipramine (Norpramin)
Doxepin (Adapin, Sinequan)
Imipramine (Tofranil, Janimine)
Iprindole
Maprotiline (Ludiomil)
Nortriptyline (Aventyl, Pamelor)
Protriptyline (Vivactil)
Trimipramine (Surmontil)

Tricyclic antidepressants (TCAs) have been on the market since the 1960s. These drugs were the most commonly prescribed antidepressants until the late-1980s, when selective serotonin reuptake inhibitors (SSRIs) were introduced. TCAs work by inhibiting the reabsorption (or, reuptake) of three neurotransmitters in the brain that can affect mood and behavior, namely serotonin, norepinephrine, and, to a lesser extent, dopamine. Tricyclic antidepressants are named for their chemical structure, which contains three rings of atoms.

Nowadays, TCAs are used mainly in very low doses at night to help with pain and to restore natural sleep patterns. TCAs work as an analgesic (pain reliever) for many neuropathic pain syndromes (pain resulting from disturbances in your nervous system). They can also help people with problems sleeping—including those with fibromyalgia, a syndrome that causes fatigue, generalized weakness, and pain amplification—to regain normal sleep regimens.

TCAs are less selective than other antidepressant medications in the cells that they affect. For example, TCAs also block certain cell receptors in your brain, which can cause certain side effects. The potential side effects of TCAs include drowsiness, dry mouth, changes in appetite, impaired thinking or confusion, blurred vision, constipation, water retention, dizziness, impaired sexual function, increased heart rate, headache, low blood pressure, sensitivity to sunlight, weight gain, nausea, and weakness.

People with narrow-angle glaucoma or an enlarged prostate should avoid TCAs, and those with a history of seizures or thyroid problems should use them with caution. Speak to your doctor if you experience any of these conditions; only she/he can decide whether TCAs are the right choice for you.

If you are pregnant, may become pregnant, or are breast-feeding, speak to your doctor about whether continuing therapy with TCAs is right for you.

Selective serotonin reuptake inhibitors (SSRIs)

Citalopram (Celexa)
Escitalopram oxalate (Lexapro)
Fluoxetine (Prozac, Sarafem, Symbyax)
Fluvoxamine (Luvox, Fevarin, Dumyrox)
Paroxetine (Paxil, Pexeva)
Sertraline (Zoloft)

Selective serotonin reuptake inhibitors (SSRIs) are usually preferred over other antidepressants because they are associated with fewer side effects. These medications are particularly helpful in the early stages of depression, and some studies suggest that SSRIs are most useful for people with more minor forms of depression. SSRIs work by preventing the reuptake (reabsorption) of serotonin by nerve cells (neurons) in the brain. In doing this, SSRIs cause more serotonin to be available in the brain for the sending of nerve impulses (neurotransmission), improving mood. The term “selective” stems from the fact that these medications work only to affect serotonin and not other neurotransmitters.

SSRIs generally come in tablet form. Some are available as extended- or controlled-release tablets, usually labeled XR or CR. In addition to causing fewer side effects than other antidepressants, SSRIs are generally less likely to interact with other medications, and they are less harmful in the event of an overdose. Most SSRIs share the same side effects and mechanism of action, but some do have different chemical characteristics, meaning your body may respond differently to different SSRIs. For this reason, it may be beneficial to try a different SSRI if one causes certain side effects or does not work particularly well for you.

Side effects of SSRIs include nausea, impaired sexual function or desire, headache, diarrhea, nervousness, rash, agitation, restlessness, increased sweating, weight loss or gain, drowsiness, or insomnia. If you experience nausea from your medication, you may benefit from trying a controlled-release tablet instead. In addition, be sure to speak to your doctor about any other medications you may be taking, especially other medications that may affect serotonin levels such as St. John’s wort. Very high levels of serotonin in the brain, which can occur when SSRIs interact with other antidepressants, can cause something called “serotonin syndrome.” Signs of serotonin syndrome include confusion, restlessness, hallucinations, extreme agitation, fluctuations in blood pressure, increased heart rate, nausea, vomiting, fever, seizures, and coma. This rare but serious side effect requires immediate medical attention. For this reason, you should not take any other form of antidepressants while taking SSRIs or within two weeks of each other, without the knowledge and permission of your doctor.

In addition, be sure to speak with your doctor if you are pregnant or may become pregnant. Certain SSRIs, namely Paxil, have been associated with birth defects. In 2006, the FDA issued a warning that women taking SSRIs during pregnancy—especially after the first 20 weeks—were at a risk for persistent pulmonary hypertension, a condition that makes it difficult for your newborn baby to breath outside the womb.

Serotonin and norepinephrine reuptake inhibitors (SNRIs)

Duloxetine (Cymbalta)
Venlafaxine (Effexor)
Desvenlafaxine (Pristiq)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressants that are used to treat depression and certain anxiety disorders. They work by inhibiting the reabsorption (reuptake) of certain neurotransmitters associated depression, namely serotonin and norepinephrine. In doing this, SNRIs increase neurotransmission (communication) between the nerve cells in your brain and thus help to elevate mood. SNRIs are generally believed to cause fewer side effects than older antidepressant medications such as tricyclic antidepressants. However, SNRIs do have some potential side effects, including nausea, vomiting, dizziness, insomnia, drowsiness, trouble sleeping, abnormal dreams, impaired sexual function and desire, headache, constipation, excessive sweating, dry mouth, tremor, gas, anxiety, agitation, and abnormal vision.

Like SSRIs, SNRIs can also cause “serotonin syndrome” if taken in conjunction with or within two weeks of other medications that increase serotonin in the brain, including St. John’s wort. Serotonin syndrome requires immediate medical attention and can cause confusion, restlessness, hallucinations, severe agitation, fluctuations in blood pressure, increased heart rate, nausea, vomiting, fever, seizures, and coma.

In addition, you should not take venlafaxine (Effexor) if you have uncontrolled high blood pressure or high cholesterol, since this medication is known to raise blood pressure and cholesterol levels, even in healthy individuals. Your doctor may recommend that you get additional blood pressure and cholesterol checks, even if you experience normal levels. In addition, people who have narrow-angle glaucoma or raised intraocular pressure should also avoid all SNRIs.

If you are pregnant or may become pregnant, you should talk to your doctor about whether SNRIs are right for you. These medications have been deemed category C drugs by the FDA, meaning they have shown side effects to the fetus in animal studies but have not been adequately studied in pregnant women. You and your doctor should decide together upon the appropriate course of treatment during pregnancy. SNRIs should be avoided during the third trimester to avoid certain complications in your baby. Evidence suggests that SNRIs taken after the twentieth week of pregnancy increase the risk of persistent pulmonary hypertension, a condition that makes it more difficult for your newborn baby to breath outside the womb.

Lithium (Eskalith, Lithobid)

Lithium (Eskalith, Lithobid) is used to treat manic depression, a condition characterized by severe mood changes, ranging from a state of excitement and elation to feelings of severe sadness and depression. Lithium works to reduce the frequency and severity of manic-depressive states, but it is not yet known exactly how lithium works to help stabilize a person’s moods. However, it is known that lithium alters the flow of sodium through nerve and muscle cells in the body, interferes with the production and uptake of certain neurotransmitters, affects the concentrations of tryptophan and serotonin in the brain, and interrupts the signaling of dopamine receptors in the brain. Lithium has been used to treat manic depression since the 1950s, and the most common preparation, lithium carbonate, was approved by the FDA in the 1970s. The effects of the medication are usually felt after about 1 week of treatment, but it can take up to 3 weeks to feel the full benefits.

Before starting treatment with lithium, be sure to tell your doctor if you are on a low-sodium diet, since lithium interferes with the regulation of sodium and water levels in the body. Be sure to drink plenty of water throughout the day. In addition, you should always take lithium with food (to prevent stomach upset) and at the same time(s) every day to keep the amount of drug in your body at a constant level.

Lithium can cause certain side effects. The most common side effects include hand tremor, dry mouth, altered taste, weight gain, increased thirst, increased frequency of urination, impotence, decreased sexual desire, and kidney abnormalities. Nausea, vomiting, and diarrhea can also occur but usually disappear as therapy continues. Taking the medication with food can help to alleviate some of these gastrointestinal side effects. Lithium can also cause low blood pressure and decreased heart rate. Approximately 1 in 25 people taking lithium develops an enlarged thyroid gland (goiter); low thyroid levels (hypothyroidism) have also been reported. Signs of this condition include dry skin, hair loss, hoarseness, increased sensitivity to cold, and swelling of the feet, lower legs, or neck.

Once you start treatment, your doctor should work with you to monitor the amount of lithium in your blood. If lithium blood levels get too high, your dosage should be reduced. Certain signs of high blood lithium levels include loss of appetite, vision problems, exhaustion, muscle weakness, muscle twitches, tremor, unsteady walking, confusion, seizure, arrhythmias, slurred speech, and coma. Once your lithium dosage is stable, you should get blood tests every month, kidney function tests every 3-6 months, and thyroid function tests every year.

Lithium can interact with many medications, including some commonly prescribed in lupus treatment. These medications include most blood pressure medications, NSAIDs, and some other medications (e.g., antidepressants). For this reason, be sure to tell your doctor of any medications you may be taking before starting treatment with lithium.

If you are pregnant or may become pregnant, you should not take lithium, since studies in pregnant women have shown a serious risk to the fetus. In addition, since lithium is secreted into the breast milk, women who are breast feeding should be very careful when taking lithium. Your doctor can advise you on the best course of treatment if you are pregnant, may become pregnant, or are breastfeeding.

Bupropion (Wellbutrin, Zyban)

Bupropion (Wellbutrin, Zyban) is another type of antidepressant classified as a norepinephrine and dopamine reuptake inhibitor (NDRI). NDRIs work by preventing the reuptake of these neurotransmitters in the brain, which in turn elevates mood. Bupropion is used to treat clinical depression and seasonal affective disorder (SAD) and is sometimes implemented in smoking cessation. It can be prescribed either alone or in combination with other antidepressant therapies, such as SSRIs. The exact mechanism of action of bupropion in the brain is not known, but it is thought to work differently than other antidepressant medications.

Side effects of bupropion are generally similar to SSRIs and SNRIs and can include agitation, dry mouth, insomnia, headache, nausea, constipation, and tremor. 4 out of every 1,000 people taking bupropion in doses of less than 450 mg/day experience seizures, and this risk increases by ten times in doses exceeding this amount. Bupropion can also increase blood pressure, so be sure to speak with your doctor if you have hypertension. In addition, be sure your doctor knows about other medications that you may be taking, especially other antidepressants.

If you are pregnant or may become pregnant, talk to your doctor about whether you may take bupropion. One study has suggested a small link between bupropion use in the first trimester and the risk of congenital abnormalities, but other studies must be performed to accurately evaluate this risk. Nursing mothers should avoid bupropion because it is secreted into breast milk.

Other Antidepressants
Mirtazapine (Remeron)
Trazodone (Desyrel)