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Antidepressant Medications

Antidepressant medications are primarily used in the treatment of major depression and anxiety. They work by gradually changing the balance of certain chemicals in the brain called neurotransmitters. Most antidepressants work to increase the amount of neurotransmitters present. The brain naturally removes neurotransmitters through a process called reuptake and some of most popular antidepressant medications block reuptake, thereby raising the concentration of specific neurotransmitters.

Role of Neurotransmitters

Several kinds of neurotransmitters are involved in behavior and mood regulation. Serotonin, dopamine, and norepinephrine are among the most significant of these chemicals.

  • Serotonin (5-HT): Serotonin is produced in the gastrointestinal tract and central nervous system. It is thought to enhance mood and alertness. Overall, it is responsible a variety of functions, including gastrointestinal tract mobility as well as cardiovascular and several organ functions.
  • Dopamine (DA): Dopamine is responsible for happiness, alertness, and body posture and orientation.
  • Norepinephrine (NE): Also known as noradrenaline, this neurotransmitter produces alertness. 

Our nervous system naturally removes neurotransmitters through a process called reuptake. In the reuptake process, the neurotransmitters are removed from the synaptic clefts of several neurons for the purpose of recycling and removal. Because of this process and each individual’s chemical makeup, a particular concentration of neurotransmitter might decline to improper levels.

A Brief History of Antidepressants

Before the 1950s, addictive opioids, amphetamine, and methamphetamines were normally used to treat cases of depression. The biogenic amine hypothesis, given in the early 1950s, suggested that a lack of 5-HT—or serotonin—and norepinephrine was detected in patients experiencing depression. Then, in 1951, researchers discovered that monoamine oxidase inhibitor drugs produced mood elevation in people. Iproniazid (Marsilid), originally developed to treat tuberculosis, was the first drug used to treat depression in the mid-1950s. 

Antidepressant Medications Currently on the Market

How Antidepressants Work

Each classification of antidepressants work slightly differently and can produce different treatment results.

  • SSRIs: SSRIs block the reuptake process of serotonin, or 5-HT. Increased serotonin concentration improves mood and alertness leading to increased interest and activity. SSRIs have the lowest number of side effects and reported adverse drug reactions. SSRIs are also used for generalized anxiety, posttraumatic stress, seasonal affective disorder (SAD), premenstrual dysphoric disorder, and bulimia nervosa (only fluoxetine). Usually, results come in 2-12 weeks depending on the condition and severity of the depression and/or anxiety. SSRIs are available in oral tablet forms.
     
  • SNRIs: Like SSRIs, SNRIs block the reuptake of NE and 5-HT. These agents produce dual action by increasing the concentration of both neurotransmitters. SNRIs are more potent and usually prescribed to people who do not recover with SSRIs. Neuropathic pain associated with diabetic neuropathy and depression, such as backache and muscle pain, can also be treated with SNRIs and TCAs. SNRIs are available in oral tablet forms.
     
  • TCAs: Tricyclic antidepressants have similar effects to SNRIs but they act wildly on cholinergic, muscarinic, histamine, and adrenergic receptors. Thus, they produce more side effects. TCAs are available in oral tablet and capsule forms.
     
  • MAOIs: MAOIs inhibit the activity of an enzyme called monoamine oxidase (MAO). This enzyme breaks down dopamine leading to its decreased concentration in the body. Inhibition of monoamine oxidase increases the amount of dopamine, which triggers the sensation of happiness and alertness. MOAIs are available in tablet and transdermal patches (such as selegiline) forms.
     
  • Aminoketones: Aminoketones are weak reuptake inhibitors of norepinephrine and dopamine. However, the latest research shows they are better in the inhibition of the uptake process of dopamine than norepinephrine. Bupropion is the only agent in this category. It is used to help the person quit smoking by alleviating the withdrawal symptoms of smoking and associated depression.
     
  • Triazolopyridines: Triazolopyridines have a weak inhibition property for serotonin—or 5-HT—reuptake. In long-term use, these agents block presynaptic 5-HT2A receptors. This increases the concentration of serotonin in the body. However, this category of drugs produces some severe adverse effects including orthostatic hypotension, sedation, cognitive slowing, and dizziness.

Side Effects

Side effects are normal with antidepressants. Common side effects include headache, nausea, insomnia, agitation, and sexual performance problems. Usually, these side effects are not severe. In addition, most side effects occur in the first few weeks of treatment and diminish over time. Doctors can adjust medication dosage levels or switch to a different medication if side effects interfere with basic functioning. 

  • TCAs, specifically, are known to produce strong cholinergic side effects such as dry mouth, nausea, urinary retention, arrhythmias, and dizziness. At higher doses, TCAs might cause life threatening arrhythmia. Loss of libido, anorgasmia in women and erectile dysfunction in men, and weight gain are commonly reported adverse effects. Sexual problems caused by TCAs are generally reported less than with SSRIs. Orthostatic hypotension can also be a major side effect in elderly people.
     
  • SSRIs may result in sexual problems, as previously mentioned, but they have fewer adverse effects than TCAs. SNRIs also produce similar side effects, but their side effects are often also less severe when compared to TCAs.
     
  • MAOIs have a common, yet potentially dangerous possibility of producing postural hypotension. Postural hypotension is the medical term for the dizzy or light-headed feeling that occurs sometimes when you stand up too fast or stretch too suddenly. Some MAOIs may cause sedation and must be taken with care when you have a tyramine-rich diet, such as, but not limited to, high concentrations of red meat, chocolate, some pork products, and most cheeses.
     
  • Aminoketones may cause seizures, nausea, vomiting, and gastric disturbances.
     
  • Triazolopyridines also have similar effects, but they might also result in postural hypotension.

FDA Warning on Increased Suicide Risk with Antidepressant Use

In 2007, the U.S. Food and Drug Administration announced a request for manufacturers of antidepressant medications to update their product labels with warnings of increased risks of suicidal thinking and behavior for young adults ages 18 to 24 when beginning treatment, usually within the first couple months. The labels were allowed to include that no scientific data highlighted an increased risk of suicide for adults older than 24, and that the risk of suicide actually decreased for adults older than 65 that were beginning treatment. If you are 24 years old or younger and beginning treatment with an antidepressant, please notify your doctor of a mental health care professional if you experience thoughts of suicide so that dosage or treatment can be adjusted. Similarly, health care providers should be mindful of this increased risk and monitor those under their care if prescribing a person under 24 years of age an antidepressant. 

Withdrawal Symptoms

In most cases, antidepressants should be removed gradually from a person's treatment protocol. Suddenly stopping an antidepressant medication can lead to withdrawal symptoms and a recurrence of depression and anxiety. Other effects include nausea, vomiting, abrupt and vivid dreams, headache, pain, and major depression.

 

Abrupt withdrawal of TCAs is often associated with symptoms suggestive of a cholinergic nature—for example, dizziness, nausea, diarrhea, insomnia, and restlessness—especially if the daily dose exceeds 300 mg. Therefore, the appropriate dose should be tapered off over several days.

When Should You Stop Taking Antidepressant Medication?

Because these are prescription-only medications, you must talk to your doctor before stopping them. If the symptoms and occurrence of at least one episode of depression exists, your doctor will generally not end the prescription for six months. Always remember that your condition of depression or anxiety and withdrawal symptoms might appear after you stop these medicines.

 

Most antidepressant medications take several weeks to reach full effectiveness. According to research, cognitive therapy combined with medication has shown to be more effective than medication alone. According to the National Institute of Mental Health, most people with depression need to remain on an antidepressant for six to twelve months or longer to see the full benefits of the medication. Some people may only have a single episode of depression or anxiety, while for others depression represents a chronic, lifelong condition. Although sometimes trial and error is necessary to match a person with the right antidepressant, the overall success rate of these medications is high. Approximately 80% to 87% of people with depression respond well to their first antidepressant prescription. 

 

References:

  1. MedlinePlus. (n.d.). Antidepressants. National Library of Medicine - National Institutes of Health. Retrieved from http://www.nlm.nih.gov/medlineplus/antidepressants.html
  2. Mayo Clinic. (n.d.). Depression (major depression). Retrieved from http://www.mayoclinic.com/health/antidepressants/MH00071
  3. U. S. Food and Drug Administration. (n.d.). Understanding antidepressant medications. Retrieved from http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm095980.htm
  4. American Psychiatric Association. (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington: American Psychiatric Association.
  5. Kessler, R.C. and Walters, E.E. (1998). Epidemiology of DSM-III-R Major Depression and Minor Depression among Adolescents and Young Adults in the National Comorbidity Survey. Depress Anxiety, 7, 3–14.
  6. Delgado, P.L., Moreno, F.A., Potter, R., et al. (1997). Norepinephrine and Serotonin in Antidepressant Action: Evidence from Neurotransmitter Depletion Studies. In Briley, M., Montgomery, S.A., eds. Antidepressant Therapy at the Dawn of the Third Millennium. London: Marin Dunitz, 141–163.
  7. Emslie, G.J., Heiligenstein, J.H., Wagner, K.D., et al. (2002). Fluoxetine for Acute Treatment of Depression in Children and Adolescents: A Placebo Controlled Randomized Trial. J Am Acad Child Adolesc Psych,10, 1205–1215.

 

Last Update: 03-04-2015

 

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