Antidepressants: Complete Guidance From Experts

Depression is a clinical disorder rather than a disease. It is characterized by a wide range of symptoms that most likely signify numerous neurochemical and neuropathological conditions in the brain. Antidepressants are drugs that are used to treat a variety of diseases and can help with the symptoms of depression. They have been in use since the 1950s.

All antidepressants require repeated dosage over an extended period to be effective therapeutically. These drugs function by restoring the proper balance of neurotransmitters. 

There have been numerous antidepressants developed over time. Each class of medication reduces the symptoms of depression in slightly different ways. Compared to the older antidepressants, the newer ones are more well-tolerated and linked to fewer medication interactions. Let us take a closer look at these medications.

What are Antidepressants?

Antidepressants are psychiatric medications approved to treat depression. They treat various conditions:

• Major Depressive Disorder (MDD)
• General Anxiety Disorder (GAD)
• Obsessive-Compulsive Disorder (OCD)
• Panic Disorder 

Antidepressants may also be prescribed to patients with persistent (chronic) pain.

Off-label uses

The number of drugs prescribed for depression is continuously increasing. Its extensive off-label usage is one of the causes of this trend. One-third of all prescriptions are for uses that are not approved, which may involve dosage or duration variations from recommended norms.

The most common off-label uses of antidepressants include:

• treating eating disorders (bulimia)
• alleviate sleep issues
• migraine prevention
• smoking cessation
• managing chronic pain

It is important to note that off-label antidepressants should only be done under the guidance of a healthcare professional and after careful consideration of the risks and benefits.

Who Can Prescribe Antidepressants?

The medical professionals who may prescribe you to use antidepressants include:

• Your primary care physician (GP)
• Your general practitioner (GP)
• a psychiatrist
• a specialist nurse prescriber
• a specialist pharmacist

Your doctor may recommend one of the many antidepressants. In some cases, psychiatrists or other mental health specialists administer them.

How Do Antidepressants Work?

Antidepressants affect the levels and activity of neurotransmitters in the brain that regulate mood, emotions, and behavior. These are serotonin, norepinephrine, and dopamine. The exact mechanism of action varies depending on the specific class of antidepressant medication. 

• Serotonin regulates mood, appetite, sleep, and other physiological functions. Low levels have been linked to depression and anxiety disorders.
• Norepinephrine is involved in the body's stress response and is associated with increased heart rate, blood pressure, and respiratory rate.
• Dopamine is involved in the brain's reward and pleasure pathways and is associated with motivation, movement, attention, and learning.

Imbalances or abnormalities cause depression in these neurotransmitters' levels and activity.

Although various antidepressants function slightly differently, they all affect the areas of the brain linked to emotions and motivation. The mechanisms that appear to be involved in mediating this effect include:

• (a) blocking one or more types of synaptic monoamine transporters
• (b) blocking enzymes that render monoamines inactive
• (c) stimulating or blocking receptor subtypes

How Long Would Antidepressants Take To Work?

Antidepressants often take 4 to 8 weeks to start working, so please be patient! Some problems like eating and sleeping become better before your mood does. It might only take the medication a little longer to work than you think. 

While taking an antidepressant, it’s important to remember that “things can get worse before they get better.” This is because when you start taking antidepressants, your motivation sensor improves while your mood is not yet treated. This can be worrying for increased risk of suicidality. This will pass with time as the mood improves with medication. 

The doctor may advise combining two antidepressants, taking an additional medication with an antidepressant, adding psychotherapy, or using other methods to enhance your mental health to experience more relief from depression.

Speak with your doctor or a mental health professional if you've been taking an antidepressant for four weeks but haven't noticed any benefits or if symptoms worsen. 

Types of Antidepressants 

There are five main categories of antidepressants, increasing the concentration of one or more neurotransmitters. The effects and side effects of antidepressants vary.

The different types of antidepressants are:

• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)
• Tricyclic antidepressants
• Monoamine Oxidase Inhibitors (MAOIs)
• Noradrenaline and Serotonin Specific Antidepressants (NaSSAs)

Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective Serotonin Reuptake Inhibitors are the first-line treatment option for depression and the most commonly prescribed antidepressants. They work by raising serotonin levels, specifically by inhibiting neuronal reuptake. SSRIs are generally well tolerated by most people and are non-sedating.

A list of SSRIs includes:

• Fluoxetine (Visit Fluoxetine page)
• Sertraline (Visit Sertraline page)
• Paroxetine (Visit Paroxetine page)
• Citalopram (Visit Citalopram page)
• Escitalopram (Visit Escitalopram page)

Compared to Tricyclic antidepressants, SSRIs have fewer and milder side effects, fewer drug interactions, and are less likely to be linked to suicide. The side effects of SSRIs include trouble sleeping, anxiety, nausea, trembling, sexual difficulties, restlessness, and agitation.

Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs)

These are the newest class of antidepressants. Serotonin and norepinephrine reuptake inhibitors increase the amounts of active serotonin and norepinephrine in the brain. As SNRIs block serotonin and norepinephrine reuptake, more neurotransmitters are available in the tissues around nerves. The drugs in this class are:

• Venlafaxine (Visit Venlafaxine page)
• Desvenlafaxine
• Duloxetine (Visit Duloxetine page)

Compared to older antidepressants, SNRIs have fewer side effects. Side effects include nausea, fatigue, sleepiness, constipation, and dry mouth. SNRIs are usually used when SSRIs have not been successful.

Tricyclic antidepressants

These are the so-called "older antidepressants" or first-generation antidepressants. Tricyclic antidepressants (TCAs) prevent acetylcholine, serotonin, and norepinephrine from entering nerve cells. By blocking their neuronal reuptake, these drugs elevate levels of norepinephrine and serotonin. Among the members of this class are: 

• Nortriptyline
• Clomipramine (Visit Clomipramine page)
• Desipramine
• Doxepin
• Dothiepin
• Imipramine (Visit Imipramine page)
• Amitriptyline

TCAs have more undesirable side effects than newer medications. The common side effects include fatigue, dry mouth, and blurred vision. TCA overdose syndrome is a medical emergency and requires immediate treatment. 

Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors (MAOIs) are drugs that block the action of monoamine oxidase enzymes. MAOIs have a long history of use as drugs recommended to treat depression. MAOIs work by inhibiting the enzyme monoamine oxidase, which breaks down neurotransmitters such as serotonin, norepinephrine, and dopamine. This leads to increased levels of these neurotransmitters in the brain, which is thought to improve mood. MAOIs include:

• Isocarboxazid
• Phenelzine
• Selegiline
• Tranylcypromine

MAOI side effects include nausea, dizziness, drowsiness, sleep problems, and restlessness. A strict diet is necessary when taking an MAOI due to potentially fatal interactions with tyramine-containing foods and medications, such as certain cheeses, pickles, and wines, as well as some painkillers, decongestants, and specific herbal supplements.

Noradrenaline and specific Serotonergic antidepressants

Mirtazapine and Mianserin are examples of Noradrenaline and specific Serotonergic antidepressants (NaSSAs). Mirtazapine is a medication used to treat depression and anxiety disorders. It blocks particular receptors in the brain that are usually activated by the neurotransmitters serotonin and Noradrenaline. By blocking these receptors, Mirtazapine increases the release of both neurotransmitters, leading to increased levels in the brain.

Besides depression, Mirtazapine is particularly effective in improving sleep and increasing appetite. This is thought to be due to its action on histamine receptors in the brain. Mirtazapine blocks histamine receptors, which can cause sedation and hunger. These effects are often used to improve sleep in patients with depression and who have lost weight. 

These antidepressants have side effects that are comparable to those of SSRIs and SNRIs. They typically have few adverse sexual effects, although they could make you gain weight. Side effects include drowsiness and sleepiness.

Effectiveness of Antidepressants

Antidepressants frequently work well. Yet, each person's response to medication varies. The Institute for Quality and Efficiency in Health Services reports that within 6-8 weeks, 40-60% of those who took an SSRI or SNRI for depression experienced some symptom alleviation. 

Research shows that antidepressants may be more beneficial for treating severe depression. Unless other therapies like cognitive behavioral therapy have failed, they are typically not advised for mild depression.

How To Choose The Right Antidepressants?

Each of the Antidepressants has a different mechanism of action and a unique set of side effects. Your healthcare professional may consider the following factors when deciding on an antidepressant that will likely be effective for you:

• Your specific symptoms: Some antidepressants may work better than others to treat depression symptoms.
• Possible side effects: Antidepressant side effects vary from drug to drug and person to person. It can be challenging to continue treatment if there are bothersome side effects such as dry mouth, nausea, weight gain, or sexual adverse effects. Talk about any side effects that could occur with your doctor or pharmacist.
• This is not true in pregnancy or breastfeeding: The balance of risks and benefits determines whether antidepressants should be used during pregnancy and breastfeeding. Specific antidepressant use during pregnancy is not advised, including paroxetine. Talk to your healthcare professional to determine the best strategy to manage your depression if you are pregnant or breastfeeding.
• Interaction with other medications: When used with other drugs, some antidepressants can have undesirable side effects.
• Other health conditions: If you have certain physical or mental health disorders, some antidepressants may pose problems for you. Some antidepressants may also aid in treating other physical or mental health issues.

Are There Any Differences Between Antidepressants?

The effects of antidepressants vary from patient to patient, and any clinical difference can only be determined after using it according to its therapeutic duration. 

As each antidepressant targets specific classes of neurotransmitters in the brain associated with depression, the effects are slightly different. Hence, differences in the side effect profiles too. Ultimately, first-line antidepressants, i.e., SSRIs, will be prescribed before other antidepressants are considered.

Possible Side Effects Of Antidepressants

Side effects are undesirable effects that follow the administration of the medication. After using the medicine for a while, some side effects can go away. If you have experienced any worrying side effects, talk to your doctor. 

Precautions of Antidepressants

Precaution is necessary for the safe use of antidepressants. When used as prescribed, antidepressants are a safe and effective therapy choice for many mental health conditions. Things you should tell your doctor before using antidepressants -

• If you use other medications,
• If you consume alcohol, 
• You are under the age of 18, 
• You have certain medical conditions, 
• You are pregnant or breastfeeding.
• Especially when you first begin taking them, several antidepressants can cause dizziness, drowsiness, and blurred vision. Do not operate machinery or vehicles while using these medications.
• Discuss changing to an antidepressant with fewer side effects with your doctor.
• Alcohol intake can reduce the effects of some antidepressant medications. 
• Moreover, taking SSRIs or SNRIs with blood thinners, prescription opioids, or antihistamines included in numerous over-the-counter cold and allergy medications, sleep aids, or anti-inflammatory medications might result in dangerous drug interactions.
• Children and young adults who take certain antidepressants may be more likely to develop suicidal thoughts. Before you start the medication, discuss a treatment and behavioral monitoring plan with your child's doctor. 

How To Get Off Antidepressants?

Before you stop using antidepressants, consult your doctor. It would be best if you did not abruptly stop using antidepressants. It is to prevent withdrawal symptoms you might have if you stop taking antidepressants suddenly. Some withdrawal symptoms include

• restlessness
• difficulty sleeping
• unsteadiness
• sweaty 

having an electric shock-like sensation in your brain and feeling agitated, fearful, or confused. After quitting the medication, withdrawal symptoms often begin within five days and linger for one to two weeks. The drug should be tapered off gradually, typically over four weeks, but occasionally longer. 

There are alternative options, such as switching back to another antidepressant from the same class and lowering the dosage gradually.

Making Antidepressants Work For You?

To optimize the effects of an antidepressant:

Be patient.

After you and your doctor have decided on an antidepressant, you might feel better in a few weeks, but it might take six or more weeks to start working effectively. You can immediately take the entire dose of some antidepressants, but you may need to increase the amount gradually.

Take your antidepressant as directed.

Before making any adjustments, call your healthcare practitioner if your medication doesn't seem to be working or if you have bothersome side effects.

Check if the side effects improve.

Many antidepressants have side effects, although they usually get better over time. For example, when taking an SSRI for the first time, you may experience dry mouth, nausea, loose stools, headaches, and insomnia.

Consider psychotherapy.

If you have mild symptoms of depression, some doctors may advise psychotherapy (talk therapy) as a first-line treatment rather than taking antidepressants. We also know it is more beneficial to take an antidepressant alongside psychotherapy than to take an antidepressant alone. It may also aid in preventing the recurrence of your depression once you've recovered. 

Try alternatives if it doesn't work well.

Talk to your doctor about modifying the dose, trying a different antidepressant, adding a second antidepressant, or taking another medication if you experience bothersome side effects or see no improvement in your symptoms after a few weeks. 

Avoid using recreational drugs and alcohol.

Although alcohol or drugs may relieve the symptoms of depression, in the long run, these drugs worsen the condition and make it difficult to manage.

Continue your antidepressants.

Take the medication as directed. If you reach a therapeutic dose, your doctor will ask you to continue taking the antidepressant for at least six months. Don't stop taking the medication if you feel better until your doctor says.

Avoid Drug Interactions

Some antidepressants can interact with other medications, and some can cause adverse reactions after it is combined with a few drugs or herbal supplements.

• Antidepressants and alcohol will affect your coordination, judgment, reaction time, and motor skills. Driving or performing other duties that require concentration and focus may become difficult or impossible.
• When used with clonidine, tricyclic antidepressants may prevent its antihypertensive effects, which can lead to increased blood pressure.
• Mixing TCAs with carbamazepine may cause lower blood levels of TCA and greater levels of carbamazepine, which could reduce the effectiveness of the TCAs or enhance the toxicity of the carbamazepine.
• Avoid taking benzodiazepines or opioids with TCAs or mirtazapine due to the increased sedative effects. Avoid using SSRIs or MAOIs in combination with medications that elevate brain serotonin levels due to the possibility of serotonin syndrome, which can be fatal. Take MAOIs and other antidepressants or drugs that increase serotonin at least 14 days apart (this should be done under a doctor’s supervision)
• MAOIs are notorious for drug and food interactions. Always check with your pharmacist or doctor before taking any other medications with MAOi. It would be best to ask for a food list to avoid when taking this medication.

Bottom Line From Practical Anxiety Solutions

We all experience depression and anxiety to some extent, so serious issues might occasionally be neglected. Antidepressant medications relieve depression and anxiety. They also aid in treating other ailments, such as bulimia and persistent pain. 

These medications often work best when combined with talk therapy, support from family and friends, and self-care practices like regular exercise, a healthy diet, and adequate sleep.

When choosing antidepressants, your doctor considers your symptoms, health issues, other medications you take, and what has previously worked for you. Antidepressants typically take a few weeks or longer to become fully effective and to reduce their initial side effects. 

Despite having distinct mechanisms of action, antidepressant medications of different classes have comparable efficacy. The decision is, therefore, dependent on the undesirable side effects. There isn't a perfect drug that can be used to treat a condition without causing any side effects. Understanding the causes of depression would help researchers develop more logical antidepressants and comprehend the limitations of already available medications.