Antidepressants

What are antidepressants?

Antidepressants are a group of medications that are often used to treat mental health disorders in which depression or low mood is a symptom, such as major depressive disorder, as well as being commonly used to treat other conditions, including anxiety disorders and posttraumatic stress disorder (PTSD) ^[1].

Symptoms of depression may include ^[2]:

• Low mood
• Feeling empty and hopeless
• Feeling guilty or worthless
• Social withdrawal
• Loss of interest in previously enjoyable activities
• Low energy levels
• Feeling the need to sleep much more than usual
• Sleep disturbances such as insomnia and waking very early
• Changes in appetite, either eating much more or much less than usual
• Thoughts of suicide
• Self-harming behaviors

There are several types of antidepressant medication, each of which works in a slightly different way in the brain. Antidepressants can be prescribed to treat various mental health conditions, including depression and anxiety disorders, as the various types of antidepressant medication impact different symptoms, along with producing slightly varying side effects ^[3].

People often respond differently to different medications, so what works well for one person may not be effective for another. As such, many people need to try more than one medication, or a combination of medications, to find the most effective treatment for their symptoms ^[4].

Types of antidepressants

There are many different types of antidepressants, all of which work by impacting the action and transmission of various neurotransmitters in the brain to affect and regulate mood ^[1]. Each type of antidepressant has a slightly different action, so produces slightly different side effects and may differ in their effectiveness of reducing particular symptoms ^[3].

SSRIs

Selective serotonin reuptake inhibitors (SSRIs) are typically the first choice of medication to treat symptoms of depression as they are generally effective and safe for both adults and children. SSRIs are known to cause fewer side effects than older antidepressants such as TCAs and have a low risk of drug interaction ^[1].

SSRIs work by reducing the reuptake of serotonin, thereby increasing the concentration of serotonin in the brain. Research suggests that serotonin is one of the neurotransmitters that is directly related to depression, with low levels of serotonin believed to cause low mood ^[5].

SSRIs do not have much effect on other neurotransmitters, so although they increase serotonin, thus improving mood, they do not impact norepinephrine or dopamine, like certain other antidepressants ^[3].

Commonly prescribed SSRIs include:

• Fluoxetine
• Citalopram
• Escitalopram
• Sertraline
• Fluvoxamine
• Paroxetine

SNRIs

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are also a commonly prescribed type of antidepressant, due to their high effectiveness and low risk of side effects ^[1].

Similar to SSRIs, SNRIs impact serotonin levels, but also have a similar action on norepinephrine by reducing the reuptake of this neurotransmitter and thus increasing the concentration in the brain ^[6].

Low norepinephrine levels are believed to cause certain symptoms of depression, so the combination of effects on serotonin and norepinephrine allows for very effective treatment of depression, especially severe depression, with fewer side effects than older antidepressants such as TCAs ^[3][6].

Commonly prescribed SNRIs include:

• Venlafaxine
• Duloxetine
• Milnacipran
• Levomilnacipran

TCAs

Tricyclic antidepressants (TCAs) were one of the first medicinal treatments developed for depression. TCAs increase the concentration of serotonin and norepinephrine in the brain, thereby reducing many symptoms of depression effectively ^[1].

They also impact cholinergic, muscarinic, and histaminergic receptors, which can increase the risk and severity of certain side effects, thus making them less tolerable than the newer antidepressants. They also have a higher risk of overdose at lower doses than SSRIs and SNRIs, so are considered less appropriate for treatment of depression ^[7].

Because of these risks, TCAs are no longer a first-line treatment. However, they are still prescribed for treatment-resistant depression, when other medications have been unsuccessful, because of their effectiveness at reducing symptoms ^[3].

Examples of TCAs include:

• Amitriptyline
• Amoxapine
• Nortriptyline
• Imipramine
• Clomipramine

MAOIs

Monoamine oxidase inhibitors (MAOIs) were the first available treatment for depression but have since been replaced by newer medications for this use, due to their side effects, health risks, and dietary restrictions ^[1][8].

MAOIs work differently than most other antidepressants, as they don’t inhibit the reuptake of neurotransmitters, but rather prevent the breakdown of serotonin, dopamine, norepinephrine, and tyramine, thus increasing the levels of these neurotransmitters, by blocking the action of the monoamine oxidase enzyme ^[8].

Because of the action on tyramine, MAOI treatment requires dietary restrictions and cannot be taken with certain other medications, as serious health issues can occur with high tyramine levels, thus making them an undesirable treatment option. MAOIs are still approved for use if other antidepressant medications have been ineffective ^[3].

Examples of MAOIs include:

• Selegiline
• Phenelzine
• Isocarboxazid

Atypical antidepressants

There are other antidepressant medications available that do not fit into the above categories, so are sometimes referred to as atypical antidepressants ^[1]. Commonly prescribed examples of these include:

• Mirtazapine: Also increases levels of serotonin and norepinephrine but with a slightly different mechanism of action and is considered an effective treatment option ^[9].
• Bupropion: Increases dopamine and norepinephrine, so has different effects to most other antidepressants. Bupropion is typically used when other medications have caused intolerable side effects relating to sexual dysfunction, as it does not produce these effects ^[1][10].
• Trazodone: Known as a serotonin modulator, it also increases serotonin levels and is an effective treatment for depression but can cause high levels of sedation and is more often used in the treatment of insomnia. Similar to bupropion, it is known for causing fewer side effects relating to sexual dysfunction than many other antidepressants ^[11].

Side effects of antidepressants

When starting a new medication, it is common to experience side effects. All antidepressants can cause side effects when starting treatment, but these effects will usually reduce as your body adjusts to the new medication ^[12]. If any side effects persist and become problematic, it is important to contact your doctor, as you may need a reduced dose or a change of medication.

Some common side effects of most antidepressant medications include ^{[1][5][7][12]}:

• Stomach upset, including constipation, diarrhea, nausea, and vomiting
• Headache
• Sleep disturbances
• Drowsiness
• Dry mouth
• Change in appetite and weight
• Sexual dysfunction, such as reduced libido and erectile dysfunction

Suicidal thoughts

It is common for antidepressant medications to cause suicidal thoughts, particularly at the start of treatment. This risk has been found to be higher in people under the age of 25 ^[1][12].

If you or your family members notice any concerning changes in your mental state, or you have any thoughts of harming yourself, contact your doctor or mental health professional immediately.

Serotonin syndrome

Most antidepressant medications can cause a risk of developing serotonin syndrome, but this is significantly higher with MAOIs, or when combining antidepressant medications ^[1][12].

Serotonin syndrome is a potentially fatal condition that may occur when serotonin levels become too high, and causes symptoms such as ^[5][12]:

• Shaking
• Sweating
• Fever
• Muscle spasms and rigidity
• Agitation
• Confusion and disorientation
• Seizures
• Irregular heartbeat
• Coma

TCAs

Typically, the newer antidepressants, SNRIs and SSRIs, cause fewer side effects and of lower severity than the older antidepressants, such as TCAs ^[7].

Anticholinergic effects are common with TCAs because of their mechanism of action in the brain. Common anticholinergic effects caused by TCAs include ^[1][12]:

• Problems urinating
• Excessive sweating
• Heart problems such as palpitations and increased heart rate
• Blurred vision and other issues with eyesight
• Weight gain

It is important to attend all arranged appointments with your doctor during your treatment and to tell them about the side effects that you have experienced, so that they can monitor your physical and mental health and prevent or treat any serious effects that do occur.

What disorders do antidepressants treat?

Antidepressant medications are approved by the US Food and Drug Administration (FDA) for use in the treatment of ^[1][5][7]:

• Major depressive disorder
• Persistent depressive disorder (dysthymia)
• Generalized anxiety disorder
• Panic disorder
• Social anxiety disorder
• Bulimia nervosa
• Bipolar disorder (usually alongside a mood stabilizer)
• Obsessive-compulsive disorder (OCD)
• Treatment-resistant depression
• Posttraumatic stress disorder (PTSD)

Sometimes medications are prescribed for uses that have not been approved by the FDA but have been deemed necessary for treatment by a medical professional, which is known as off-label use. Off-label uses of some antidepressants include ^[13]:

• Eating disorders
• Fibromyalgia
• Body dysmorphic disorder
• Autism

TCAs are often prescribed off-label for ^[7]:

• Chronic pain conditions
• Migraines
• Insomnia

Mirtazapine is often prescribed off-label for ^[9]:

• Insomnia
• Various anxiety disorders
• PTSD
• Migraines

Trazodone is also commonly prescribed off-label for insomnia ^[11].

Alternative treatments for depressive disorders

Often the most effective treatment for depression is a combination of medication and talking therapy ^[3]. Your doctor can discuss with you the available treatment options for your condition.

Medications

People respond differently to different medications, so to treat depression or other disorders in which similar symptoms may occur, you may need to try several medications or a combination of medications before you find the most effective treatment.

Sometimes, depression is resistant to treatment with antidepressant medications and may require the use of other medications to effectively manage the symptoms. This might include the use of mood stabilizers, antipsychotics such as risperidone and olanzapine, or stimulants such as methylphenidate ^[3][4].

It is important to take medication exactly as prescribed by your doctor, without missing doses, taking more than is prescribed, or suddenly stopping a medication, as adverse effects can occur.

Therapy

Talking therapies can help to manage emotional distress that can occur with mental health conditions, and it is advised to engage in therapy alongside medication, for the most effective treatment. Various types of therapy are available, such as ^[4][14]:

• Talk therapy: Cognitive behavioral therapy (CBT) is one type of talk therapy that has been shown to be an effective treatment for depression and can help to provide a better understanding of your condition, increase tolerance to emotional distress, and alter negative thoughts and behaviors.
• Family therapy: Family therapy can help you and your family better understand your condition and talk about any issues that may occur, while providing your family members with support and education about how to help you manage your symptoms.
• Group therapy: Speaking with others who have had similar experiences can help you to understand and accept your condition, teach you new skills in managing your symptoms, and reduce negative emotions.

Self-help

Looking after your general well-being can help you to manage the symptoms of your condition, by improving and maintaining your physical and mental wellbeing with self-help techniques, such as ^[2][4][14]:

• Healthy eating
• Avoiding drugs and alcohol
• Relaxation activities, such as meditation, breathing exercises, or yoga
• Forming and maintaining a regular sleep pattern
• Engaging in regular exercise
• Consistently attending appointments with your doctor and mental health professionals
• Ensuring you follow advice and treatment plans