What is the Mechanism of Action and How Do Antidepressant Drugs Work
Generally speaking most drugs (excluding replacement therapies) don’t have any intrinsic properties that alleviate the targeted symptoms but rather assist the body in regulating its own chemistry through differing mechanisms. How do antidepressant drugs work? Antidepressants work by controlling the balance of the neurochemistry in the brain. There are three chemicals referred to as neurotransmitters: serotonin (5HT or 5-hydroxytryptamine), norepinephrine (NE), and dopamine (DA). Each class of antidepressant has a mechanism that works to increase the levels of these neurotransmitters. Each class has various side effects associated with them. Most psychiatrists do not ignore any of these because sometimes patients may not respond or have problematic side effects to the newer medications and will respond to the older ones much better. The newer SSRIs and SNRIs typically begin to work faster with fewer side effects. Do antidepressants really work? Yes, they are very effective although, there is always a small segment of the population that is treatment refractory and don’t respond to the medication in which case we have other forms of treatment. Most antidepressants take about four weeks to show their full effect and reach their therapeutic levels. Too often a patient will stop taking a medication because they don’t feel its effects or they don’t like the side effects. This must be avoided because often a psychotropic medication will have no therapeutic benefit until a certain minimum level has been achieved in the body; additionally side effects will often subside within a few weeks.
These drugs usually don’t work gradually but have definite minimum doses and times periods before any therapeutic effects are experienced. When the right medication is found, it is my goal that a patient not have bothersome side effects and that the patient only have a resolution of their depressive symptoms. In fact, this is generally the case. How do newer antidepressant drugs work compared to the older tricyclics? Most of the time the SSRIs and SNRIs are faster acting and more effective with fewer side effects. The older medications had many more side effects and had the tendency for the therapeutic benefits to dissipate over time and required increasing the dosing. SSRIs have been discovered to protect the brain from damage. The hippocampus region of the brain is sometimes damaged and loses size from depression. SSRIs have been known to act as a catalyst (neurogenesis) and assist stem cells in transforming into adult brain cells thus restoring the hippocampus. This region of the brain is responsible for memory.
We can’t cure depression or anxiety with the medications, (though scientists are devoting much research to find the causes and cure for depression through genetic engineering); but we can control these illnesses while one is taking the medication. The sooner the medication is used to treat the depression, the better the chances of treating the depression and minimizing the condition. This is why it is important to discuss with your doctor the problems or reasons why you want to come off of the medication. Too often patients begin to feel normal as the symptoms subside and want to stop the medication abruptly. This often leads to a relapse and in some cases severe side effects from not tapering down on the dose. The brain just like any organ can become diseased. These medications correct the chemical imbalance causing the depressive symptoms, thus resulting in a resolution of the depression. Antidepressants to the brain are like insulin to the pancreas.
How do Antidepressant Drugs Work Compared to the Older Tricyclics and other Medications
Opiates were used up until the late 1950’s and amphetamines through the late 1960’s, but due to the risk of addiction, they fell out of favor. During the early 1950’s, MAOI (monoamine oxidase inhibitors – MAOI is plural) were introduced. The MAOI were first introduced as anti-tuberculosis drugs and are still a mainstay treatment of TB. Once the brain’s three neurotransmitters have played their part in sending messages in the brain, they get broken down and then disposed of by a protein in the brain called monoamine oxidase, a liver and brain enzyme. These MAOI work by blocking this activity. They block the degradation of the monoamine neurotransmitters by inhibiting the enzyme monoamine oxidase, leading to increased concentrations of these neurotransmitters in the brain; and an increase in neurotransmission. When the excess neurotransmitters don’t get destroyed, they start accumulating in the brain. Since depression is associated with low levels of these monoamines, increasing the monoamines ease depressive symptoms. MAOI lost their popularity due to their potentially severe side effects. The major side effect was caused by the increase in tyramine, which can lead to a very serious side effect if these MAOI are taken with certain foods containing tyramine. Therefore, most of the time the patient must be on a strict diet, unless they are on the MAOI patch at the lowest dose. Additionally, MAOI have many interactions with other drugs, this must be watched closely by the doctor and pharmacist.
Tricyclic antidepressants (TCA) were discovered shortly after the MAOIs, in the late 1950′s. Tricyclics block the reuptake of certain neurotransmitters such as norepinephrine and serotonin and to a much lesser extent, dopamine. They are used less commonly now due to the development of more selective and safer drugs. Side effects include increased heart rate, drowsiness, dry mouth, constipation, urinary retention, blurred vision, dizziness, confusion, and sexual dysfunction. Toxicity occurs at approximately ten times normal dosages. These drugs are often lethal in overdoses, as they may cause a fatal heart arrhythmia. However, TCA and some MAOI antidepressants are still used because of their effectiveness, especially in severe cases of major depression and when the SSRI and SNRI classes are ineffective or giving patients intolerable side effects. Some recent studies are now claiming that the side effects of serotonin uptake inhibitors SSRIs may have an impact on male fertility.
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants considered the current standard of drug treatment along with serotonin and norepinephrine reuptake inhibitors (SNRIs). Prozac, the first SSRI, was first put on the market in 1988. A possible cause of depression is an inadequate amount of serotonin, a chemical used in the brain to transmit signals between neurons. SSRIs are said to work by preventing the reuptake of serotonin by the presynaptic neuron, thus maintaining higher levels of 5-HT in the synapse and increasing the active levels of serotonin.
Serotonin and norepinephrine reuptake inhibitors (SNRIs) are the newest class of antidepressants. SNRIs increase levels of both norepinephrine and serotonin. Low levels of both neurotransmitters are associated with depression, norepinephrine is thought to be involved more with alertness and energy while serotonin influences mood. By increasing levels of both SNRIs work on different aspects of depression.
How are the Antidepressants used in a Medication Management Plans
Typically, my first line of antidepressant medications are the SNRI class of which there are several drugs available. These often begin to take effect in two to four weeks and are effective often 70% of the time. If the patient is not responding well to these, I will move to an SSRI and then if necessary possibly consider augmentation with another medication or move to the tricyclics. In recent years at my psychiatry practice in Scottsdale, I have also resorted to using MAOI, which has shown some efficacy. It is important to understand medication management with respect to augmentation as well as using some of the older medications. Some patients that are considered treatment refractory can benefit from augmentation or the use of the older TCA and MAOI. If you want to find a psychiatrist in Scottsdale or Phoenix psychiatrist, please contact me through this website or call me to set an appointment. As a policy, I leave all options on the table with regards to treatment because of the effectiveness and variety of the medications and therapies that are available today. Someone suffering from depression should seek treatment to have a resolution of their condition. New research is showing us that the sooner psychiatric illnesses are treated from the onset, the more efficacious generally the treatment and the less risk of developing treatment refractory depression in the future. The bottom line is that it is important to seek help. There are many options available to treat depression and I have just been talking about medications here. Following is a link to a good website that will explain in greater detail the antidepressant medications in the four categories that I have briefly discussed in this article. Additionally I have posted articles on other treatments for depression such as Vagal Nerve Stimulation, and TMS.