How Do Antidepressants Work?
Neurotransmitters are chemicals that send messages between cells of the nervous system. Depression is thought to be caused by decreased activity of neurotransmitters in areas of the brain which regulate mood levels and other processes. Different types of neurotransmitters may be involved in mood regulation including serotonin, norepinephrine, and dopamine. Antidepressants work to increase the supply of these neurotransmitters so that messages between the cells in these mood centers are more frequently sent, increasing activity and elevating mood.
Each of the three main neurotransmitters has different qualities and actions. These include:
Serotonin – Serotonin is considered the “satiety” hormone which helps you feel “full” after eating and helps to modulate anger, resist pain and feel rested after sleeping. Serotonin is made in the body from the amino acid tryptophan which is found in high-protein foods like meats, nuts, and beans. Increasing serotonin in the mood centers may help to increase mood levels by producing a feeling of “wellness” and “satisfaction”.
Norepinephrine – Norepinephrine is also called noradrenaline and is one of the neurotransmitters involved in the “fight or flight” response that occurs in times of stress or danger. It works to increase alertness and produces increased heart rate and blood pressure. Increasing the amount of norepinephrine in the mood centers of the brain may serve to “wake” those areas and increase mood levels.
Dopamine – Dopamine is an “excitement” or “pleasure” hormone. It is normally produced during stimulating activities such as sex and exercise. Dopamine release is also caused by drugs of abuse and risky behaviors like gambling and is responsible for the euphoria that may lead to addiction. In the depressed brain, dopamine deficiency may cause disinterest in pleasurable activities and lead to depression. Increasing the activity of dopamine at moderate levels may return the ability to enjoy normal activities and increase mood level
There are a number of different types of antidepressants which work on one or more of the neurotransmitters and finding the correct medication can be challenging.
Types of Antidepressants
Antidepressants categorized on how they work. Some work by preventing the breakdown of neurotransmitters so that there are more of them for the cell to use while others work by making them stay in the synapses or spaces between the cells for a longer period of time. Types of neurotransmitters include:
Selective Serotonin Reuptake Inhibitors
When neurotransmitters are released into the synapses to send a message from one cell to another. Once the message has been sent, the neurotransmitter is gathered up to be reused the next time a message is needed. This process is known as “reuptake”.
Selective serotonin reuptake inhibitors (SSRIs) work by inhibiting or blocking the reuptake of serotonin so that it stays in the synapse for a longer period of time. SSRIs are the most popular type of antidepressant and have fewer side effects than many other antidepressants. They are used for a variety of depressive and anxiety or mood disorders.
- Prozac (fluoxetine)
- Zoloft (sertraline)
- Paxil (paroxetine)
- Luvox (fluvoxamine)
- Celexa (citalopram)
- Lexapro (escitalopram)
Serotonin-Norepinephrine Reuptake Inhibitors
Serotonin-norepinephrine reuptake inhibitors (SNRIs) blocking the reuptake of both norepinephrine and serotonin in the synapses so that the activity is increased. Like SSRIs, they have fewer side effects than older medications and are used to treat a broad variety of psychiatric disorders. They do, however, have side effects which can be bothersome in some people including increased heart rate and anxiety.
- Effexor (venlafaxine)
- Cymbalta (duloxetine)
- Pristiq (desvenlafaxine)
- Savella (milnacipran)
- Fetzima (levomilnacipran)
Tricyclic Antidepressants (TCAs) are one of the older types of antidepressants. They work by blocking the uptake of serotonin and norepinephrine and by affecting certain other receptors including histamine, sigma, and 5HT. Because they are non-specific and have a number of actions, they also have a large number of side effects, some of which can be severe or bothersome such as excess sweating, constipation, sedation, and effects on the heart. They are rarely used unless other medications have not worked.
- Adapin and Sinequan (doxepin)
- Anafranil (clomipramine)
- Aventyl and Pamelor (nortriptyline)
- Elavil and Endep (amitriptyline)
- Tofranil (imipramine)
- Norpramin (desipramine)
- Surmontil (trimipramine)
- Vivactil (protriptyline)
Atypical and Tetracyclic Antidepressants
There are several antidepressants that do not fall into any of the other drug classes. In general, they are reuptake inhibitors which may affect one or more of the neurotransmitters but may also work in other ways. They may have more side effects than specific medications, but these vary from drug to drug. They are used for depression but also may be used for other disorders such as obsessive-compulsive disorders, eating disorders, and smoking cessation.
Atypical antidepressants include:
- Wellbutrin and Zyban (bupropion)
- Ludiomil (maprotiline)
- Remeron (mirtazapine)
- Desyrel (trazodone)
- Trintellix (vortioxetine)
Monoamine Oxidase Inhibitors
Monoamine oxidase (MAO) inhibitors are the oldest class of antidepressants and are only used in extreme cases when no other medications have worked. They work by inhibiting the activity of an enzyme, monoamine oxidase, which breaks down neurotransmitters and other chemicals in the body. Because the monoamine oxidase enzyme is also used to metabolize nutrients and other medications, blocking this enzyme can result in additional problems when certain types of food, nutrients or medication are taken. Side effects can be severe and even, dangerous and medication use requires strict adherence to dietary restrictions and prevents the use of some medications.
MAO Inhibitors include:
- Nardil (phenelzine)
- Parnate (tranylcypromine)
- Marplan (isocarboxazid)
Use of Antidepressants in the U.S.
Since the introduction of Prozac in the mid-1980s, the first SSRI, antidepressant use has increased dramatically. Prozac was the first of the “newer” medications which had vastly improved side effect profiles. Use of antidepressants continues to rise with newer medications being approved on a routine basis and for an increasing number of psychiatric disorders. Between 1999 and 2014, the CDC shows a 65% increase in antidepressant use. Between 2011 and 2014, about 12% or one in eight Americans were on antidepressants at any one time.
Important Considerations for Antidepressant Use
Antidepressants are an important tool in treating a number of psychiatric disorders but they are often more effective as part of a comprehensive treatment plan. Each type of antidepressant has its own side effect profile and warning label. Some antidepressants require dietary changes or cannot be taken with other medications. In most cases, antidepressants may take several weeks to begin working and all must be taken regularly, as prescribed to be effective.
It is essential that patients maintain contact with their physician or health care provider. All medications that the patient is taking should be discussed with a doctor or pharmacist before beginning a new treatment. Changes in mood level or behavior should be discussed with the mental health professional and bothersome side effects should be reported immediately. Patients should not change or discontinue medications without discussion with a health provider.
In many cases, depression and other psychiatric or behavioral disorders are best treated with a combination approach. Many patients find that medication may not be adequate and will benefit from therapy sessions, biofeedback or behavioral modification plans. This may entail “talk therapy” with a psychologist, psychiatrist, social worker, or other counselors. The mental health care team should coordinate treatments when possible for more effective management.
All medications cause side effects. Antidepressant side effects vary widely depending on medication type and some may be bothersome or severe. Certain side effects will be worse at the beginning of treatment or when medication doses change and may go away with time. Others may become worse as medication levels are established and still others may become bothersome or severe. Bothersome side effects, those affecting level of consciousness, causing heart symptoms, pain, odd movements or dramatic changes in behavior should be reported to a doctor right away. Medication should not be changed or suddenly discontinued unless supervised by a physician.
A black box warning or boxed statement is included on all antidepressants warning of an increased risk of suicidal thoughts and behavior. This is particularly important in children, adolescents, and young adults but can affect other patients, especially at the start of treatment. Any suicidal thoughts or behaviors should be treated as a mental health emergency.
Discontinuation and withdrawal
Sudden discontinuation of antidepressants can cause symptoms of withdrawal. In some cases, sudden discontinuation may even be dangerous. In most cases, withdrawal can be minimized by slow dosage reduction over a period of time, but some symptoms may still occur. Discontinuation should be monitored by a physician.