Combining Antidepressants for Treatment-Resistant Depression - An Overview

Introduction

Depression is a typical worldwide illness that interferes with our daily activities and socioeconomic status. Research has estimated about 3.8% world's population encounters depression. So, it is comprehensible that nearly two hundred and eighty million people have depression. Several patients with depression show poor responses to solitary antidepressants or antidepressant monotherapy. Overall 10 to 15 percent of people with depression show no improvement, while 30 to 40 percent exhibit partial improvement. In that cases, approaches like combining anti-depressants proved efficacy.

What Is Treatment-Resistant Depression?

As we know, depression is a chronic mood disorder featured by a persistent feeling of sadness or demotion in the mood. Subsequently, this could cause several physical and emotional problems by interfering with our day-to-day activities. Depression is often known as major depressive disorder or clinical depression. Doctors commonly advise people with depression to take antidepressant medication. Unfortunately, some patients have unresponsiveness to the first-line treatment of antidepressants. Depression is hard to treat due to underlying conditions like unipolar disorder, bipolar disorder, and hypothyroidism. So after confirming the actual diagnosis and looking for poor responses, depression that isn’t responding to antidepressants is known as treatment-resistant depression.

What Causes Treatment-Resistant Depression?

There is no exact cause of treatment-resistant depression. Besides, several study-based theories are here to describe that.

• A misconception with other conditions.

• Genetic variations could alter the efficacy of the treatment.

• Metabolic factors like nutrients. A study shows that lower folate levels in the brain fluid might have less response.

In addition to the theories, the following risk factors could alleviate the treatment for depression.

• Patients with major depression for a long time.

• Depression shows very severe or very mild symptoms.

• Other illnesses like anxiety.

How to Identify a Treatment-Resistant Depression?

No precise tool is available to rule out treatment-resistant depression. However, the doctor will conclude the diagnosis when the patient shows no improvement in symptoms after one or two anti-depressants. Indeed, it takes six to eight weeks for the full effect of an anti-depressant. And in case of any doubt, check with the diagnosis, the medication in appropriate doses, and other conditions worsening depression.

What Are the Antidepressants Used for Treatment-Resistant Depression?

Antidepressant medication is the first-line treatment or drug of choice for depression, and a combination of antidepressants for treatment-resistant depression. They relieve depression and regulate mood by affecting specific chemicals carrying messages throughout the brain. The different classes of antidepressants are given below.

Selective Serotonin Reuptake Inhibitors (SSRI): SSRI is the chiefly prescribed antidepressant. SSRI increases serotonin, a chemical substance that carries signals between nerve cells. And also inhibits the reuptake of serotonin.

• Citalopram.

• Escitalopram.

• Fluoxetine.

• Paroxetine.

• Sertraline.

Serotonin Norepinephrine Reuptake Inhibitors (SNRI): Like SSRI, this also relieves depression by altering the action of chemical messengers involved in the regulation of mood.

• Desvenlafaxine.

• Duloxetine.

• Levomilnacipran.

• Milnacipran.

• Venlafaxine.

Norepinephrine and Dopamine Reuptake Inhibitors: like Bupropion and Mirtazapine. This aid in affecting chemical messengers like dopamine and norepinephrine.

Tricyclic antidepressants block the reabsorption of chemical messengers.

• Amitriptyline.

• Desipramine.

• Doxepin.

• Imipramine.

• Nortriptyline.

Tetracyclic Antidepressants: they contain four cyclic rings in their structure. And inhibit the reabsorption of serotonin and noradrenaline and thus elevate the mood.

• Amoxapine.

• Mazindol.

• Mirtazapine.

• Maprotiline.

Monoamine Oxidase Inhibitors: they help depression by affecting the monoamine oxidase enzyme inside the brain cell.

• Phenelzine.

• Selegiline.

• Tranylcypromine.

What Includes the Combination of Antidepressants for Treatment-Resistant Depression?

Several adjacent guidelines are proven effective in non-responders to relieve depression, such as switching to a different drug, high-dose treatment, combining anti-depressants, and adding adjuvant drugs. The following are some common combinations of medications for treatment-resistant depression.

• Combination of tricyclic antidepressant and monoamine oxidase inhibitor.

• Combination of newer generation antidepressants such as Bupropion and Mirtazapine, a class of norepinephrine and dopamine reuptake inhibitors.

• A combination of Mirtazapine and Venlafaxine was proven to be safe.

• Bupropion is often added to selective serotonin reuptake inhibitors (SSRI) or selective norepinephrine reuptake inhibitors (SNRI).

• Trazodone, a serotonin modulator, is combined with SSRIs to tackle insomnia that may occur due to treatment with SSRIs.

• And other combinations of different or the same classes of anti-depressants.

Which Combination of Antidepressants Is Effective?

Many evident based clinical-trials and studies verified antidepressant combination therapy is more efficient than other combinations and monotherapy. Similarly, one particular combination is proved as superior to other combinations for treating major depression. Combining antagonists of presynaptic alpha2-autoreceptors with reuptake inhibitors is proven to be a safe and effective first-line option.

What Is an Augmentation Treatment?

The doctor would add other, unlike medication with the antidepressant in case of treatment-resistant against anti-depressant monotherapy. This combination would improve the symptoms in some cases than an anti-depressant itself. Here are some drugs used as augmentation treatment.

• Antipsychotics like Olanzapine, Aripiprazole, and Quetiapine.

• Lithium.

• Thyroid hormone.

• Ketamine, such as S-ketamine nasal spray.

• Dopamine drugs such as Ropinirole and Pramipexole.

• Nutritional supplements like omega-3 fatty acids, Folic acid, Ademetionine, and Zinc.

What Are the Adverse Effects of Antidepressants?

Before prescribing the combination of anti-depressants, the doctor will first consider the safety of that combination. For instance, some patients might result in serotonin syndrome when an antidepressant is combined with monoamine oxidase inhibitors. Also, some displays exacerbated tricyclic side effects while combining tricyclic antidepressants with SSRIs. However, patients have fewer problems combining multiple SSRIs and SNRIs than adding them with other classes like tetracyclines and monoamine oxidase inhibitors. The following are the common side effects of antidepressants.

• Agitation or anxiety.

• Sick feeling.

• Diarrhea or constipation.

• Indigestion.

• Dizziness.

Tricyclic side effects

• Dryness of mouth.

• Blurred vision.

• Constipation.

• Dizziness or drowsiness.

• Excessive sweating.

• Elevated heart rate.

Serotonin syndrome

This syndrome occurs when the serotonin levels are too high by SSRI or SNRI. This includes symptoms such as confusion, muscle twitching, agitation, shivering, and sweating.

Conclusion

Limited evidence and clinical trials support the efficacy of combining anti-depressants for treatment-resistant depression. Therefore, the doctor will combine anti-depressants when one has less improvement in depressive symptoms, as it is safe and effective.