What Are Antidepressants?

Antidepressants are among the most widely prescribed medications worldwide.They are used for the treatment of depression and psychiatric disorders such as obsessive-compulsive disorder (OCD), anxiety disorders, eating disorders (anorexia/bulimia), and chronic pain. Antidepressants can reduce the symptoms of depression, but do not serve as a cure for depression.

Almost twice as many women as men suffer from depression. As many as one-quarter of the U.S. population will experience at least one episode of depression during their lifetime.

An episode of major, or clinical, depression is characterized by a depressed mood most of the day for at least two weeks. Symptoms that may accompany depression are:

  • Fatigue
  • Feelings of worthlessness and guilty
  • Impaired concentration
  • Significant weight gain or loss
  • Insomnia (decreased sleep) or hypersomnia (excessive sleeping)
  • Decreased interest in activities, which is also known as anhedonia
  • Restlessness or feeling slowed down
  • Recurring thoughts of death or suicide
  • Irritability or anger
  • Drug or alcohol abuse

Depression can be triggered by life events such as:

  • Grief from losing a loved on whether it be through death, divorce, or separation
  • Social isolation
  • Major life changes such as moving, graduation, changing jobs, and retirement
  • Personal conflicts in relationships
  • Physical, emotional, or sexual abuse

Those with a previous history of depression requiring hospitalization are at a high risk for future suicide. Some studies have even proposed that severe depression increases the risk of heart disease and diabetes. The economic burden of depression in the U.S. alone is estimated at $70 billion annually. The World Health Organization (WHO) estimates that by 2020, depression will be second only to heart disease as the leading cause of disability worldwide. The majority of those suffering with depression can be effectively treated with a combination of antidepressants and counseling or psychotherapy.

Classes Of Antidepressants

Antidepressants-ProzacOver the years, many classes of antidepressants have been developed. The first class of antidepressants to be developed were the monoamine oxidase inhibitors (MAOIs). Examples of MAOIs include isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Emsam), and tranylcypromine (Parnate). The MAOIs and other antidepressants treat depression by changing the levels of one or more neurotransmitters, which are naturally occurring chemicals in the brain. The MAOIs increase the levels of the neurotransmitters norepinephrine, serotonin, and dopamine. It is this increase in neurotransmitters that boost the mood of a depressed individual.

The monoamine oxidase inhibitors are prone to adverse effects and have to be taken with dietary restrictions as they can cause dangerously high blood pressure when taken with certain foods or medications. The MAOIs have been replaced by the tricyclic antidepressants (TCAs), which cause fewer side effects and have no dietary restrictions. Examples of TCAs include imipramine (Tofranil), amitriptyline (Elavil), nortriptyline (Pamelor), and trimipramine (Surmontil). They increase the levels of the neurotransmitters serotonin and norepinephrine. Tricyclic antidepressants not only treat depression, but are also used to treat anxiety disorders and chronic nerve pain.

Antidepressants-ZoloftThe next class of antidepressants developed were the selective serotonin reuptake inhibitors (SSRIs). They work by increasing levels of the neurotransmitter serotonin in the brain. It is generally accepted in medicine today that depression is caused by decreased levels of serotonin in the brain. Examples of SSRIs include paroxetine (Paxil), fluoxetine (Prozac), citalopram (Celexa), escitalopram (Lexapro), and sertraline (Zoloft). Today, SSRIs are the most commonly prescribed class of antidepressants.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are among the newer classes of antidepressants. Examples of SNRIs include duloxetine (Cymbalta), venlafaxine (Effexor XR), and desvenlafaxine (Pristiq). They increase levels of serotonin and norepinephrine, which can boost the mood of a depressed person. This class of medications is also used to treat anxiety and nerve pain.

Norepinephrine-dopamine reuptake inhibitors (NDRIs) are another class of antidepressant. The lone NDRI is bupropion (Wellbutrin). It increases levels of norepinephrine and dopamine, which can improve mood in those who are depressed. Bupropion’s other uses include the treatment of seasonal affective disorder (SAD) and can be combined other medications to treat bipolar disorder. The drug is also marketed as Zyban, which aids in helping people quit smoking.

Atypical antidepressants don’t fit into other classes of antidepressants. Examples include mirtazapine (Remeron), nefazodone (Serzone), and trazodone (Desyrel). These medications are frequently used in severely depressed patients whose symptoms have not been helped or can’t tolerate the side effects of SSRIs.

Conditions Treated By Antidepressants

Antidepressants are primarily used to treat depression, but they can also treat other disorders such as:

  • Generalized anxiety disorder (GAD)
  • Social anxiety disorder
  • Obsessive compulsive disorder (OCD)
  • Bipolar disorder
  • Childhood bedwetting
  • Post-traumatic stress disorder (PTSD)
  • Pain, especially diabetic nerve pain
  • Fibromyalgia
  • Hot flashes associated with menopausal symptoms
  • Tourette syndrome
  • Anorexia and bulimia
  • Premenstrual dysphoric syndrome
  • Migraine headaches

Adverse Effects Of Antidepressants

Antidepressants can have various adverse effects that may include:

  • Dry mouth
  • Nausea, diarrhea, and constipation
  • Headache
  • Drowsiness
  • Dizziness
  • Weight gain or loss
  • Difficulty urinating
  • Erectile dysfunction, delayed orgasm, and decreased libido
  • Excessive sweating
  • Low blood pressure
  • Seizures
  • Insomnia
  • Tingling sensations on the skin
  • Muscle aches
  • Irregular heart rate
  • Confusion
  • Mania, which is periods of great excitement, euphoria, delusions, and overactivity in those with bipolar disorder
  • Tremor
  • Visual disturbances

antidepressantsThe tricyclic antidepressants (TCAs) are very toxic and increased doses such as those taken in a suicide attempt have a 70% mortality rate. In other words, suicide attempts involving overdoses of TCAs have a 70% success rate. The use of TCAs to treat depression is waning. They have been replaced by the selective serotonin reuptake inhibitors (SSRIs), which have a better safety profile.

Sexual dysfunction is a common adverse effect of antidepressant treatment. Antidepressant-induced sexual dysfunction may cause patients to discontinue their use, which could affect their overall well-being. Drug holidays were shown to significantly improve sexual dysfunction in depressed patients taking the SSRIs sertraline (Zoloft) and paroxetine (Paxil), but not fluoxetine (Prozac).

Another concern is antidepressant discontinuation syndrome. It affects 20% of patients who abruptly stop antidepressants after taking them for at least six weeks. Symptoms of the syndrome may include flu-like symptoms, insomnia, nausea, dizziness, sensory disturbances, and hyperarousal. It is recommended to follow the directions of a physician when discontinuing an antidepressant. A gradual decrease, or taper, when discontinuing antidepressants is recommended to decrease the chances of developing antidepressant discontinuation syndrome.

Both TCAs and SSRIs are effective in the treatment of depression when compared to placebo.  Use of antidepressants may be a risk factor for the development of type 2 diabetes, but more controlled long-term clinical trials are required. These trials need to look at individual antidepressants rather than general classes.

Conclusion

Antidepressants-Prozac-pillsThere are multiple classes of antidepressants. SSRIs are the most commonly prescribed antidepressants. Most researchers have shown an improvement in the symptoms of depression when treated with an antidepressant. Other researchers argue an antidepressant’s effect on depression is no better than placebo. This means that most of a patient’s improvement in depression is due to the placebo effect. Others feel that improvement in depression with antidepressants is statistically significant, but not clinically significant.

Regardless of the class of antidepressant used, there should be some improvement in the symptoms of depression. Some antidepressants work better than others. As a result, a trial and error approach is often utilized in the treatment of depression. Antidepressants have varied adverse effects. The balancing act is to employ an antidepressant that decreases the symptoms of depression with the fewest adverse effects.

References

  1. Ioannidis J. Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials? Philosophy, Ethics, and Humanities in Medicine. 2008; 3: 14.
  2. Wrobel S. Science, serotonin, and sadness: the biology of antidepressants. A series for the public. FASEB Journal. 2007 Nov; 21 (13): 3404-3417.
  3. Arroll B et al. Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis. Ann Fam Med. 2005 Sept; 3 (5): 449-456.
  4. Barnard K, Peveler RC, Holt R. Antidepressant medication as a risk for type 2 diabetes and impaired glucose regulation. Diabetes Care. 2013 Oct; 36 (10): 3337-3345.
  5. Razmic SG et al. Antidepressant-induced sexual dysfunction. Ann Pharmacother. 2002 Oct; 36 (10): 1577-1589.
  6. Warner HW et al. Antidepressant discontinuation syndrome. Am Fam Physician. 2006 Aug; 74 (3): 449-456.
  7. Matthew JT. Strategies for managing antidepressant-induced sexual dysfunction: a review. Current Psychiatry Reports. 2006; 8 (6): 431-436.
  8. Rothschild AJ. Selective serotonin reuptake inhibitor-induced sexual dysfunction: efficacy of a drug holiday. Am J Psychiatry. 1995 Oct;152 (10): 1514-1516.
  9. Solakovic N. Tricyclic antidepressants: old drugs-new applications. Anesth Pain. 2011; 1 (1): 15-19.