Introduction:
Depression is commonly seen among individuals who respond well to the treatment. A combination of anti-depressants and psychotherapy are standard treatments that provide relief to individuals. Treatment-resistant depression (TRD) is considered when the individuals do not respond to two different antidepressants. Most patients with major depressive disorder do not show a response to treatment. Patients try multiple therapies and suffer for months with a feeling of hopelessness and brokenness. Several strategies are available to treat treatment-resistant depression.
What Is Treatment-Resistant Depression (TRD)?
TRD is a condition in which patients with depressive disorder do not respond or persist in having depressive symptoms despite anti-depression treatment. TRD can be influenced by underlying or coexisting medical conditions, psychiatric comorbidity, and subtypes of depression. This leads to a challenging presentation of conditions for healthcare professionals or psychiatrists.
What Are the Concerns for Treatment-Resistant Depression Individuals?
Patients with TRD should share their inner experiences, lifestyle changes, questions related to risk factors or any underlying cause of TRD, better treatment options, costs and insurance coverage, duration of treatment, intolerance issues, suicidal thoughts and attempts, proper medication schedule, intolerance issues, and non-suicidal self-injurious behaviors.
Issues to be considered include adherence to treatment, the impact of medical conditions such as cancer, anemia, thyroid disease, heart disease, eating disorders, drug interactions, and other herbal supplements, genetic vulnerability, and manifestations of impending relapse. Treatment such as ECT (electroconvulsive therapy), VNS (vagus nerve stimulation), rTMS (repetitive transcranial magnetic stimulation), DBS (deep brain stimulation), and magnetic seizure therapy are addressed to patients.
What Are the Factors Contributing to Treatment-Resistant Depression?
Several factors contribute to treatment-resistant depression. They are -
-
Inadequate Treatment: Some cases of TRD may arise due to inappropriate treatment, skipping doses, unpleasant side effects, drug interactions, and wrong dosage. In such cases, reassessment of the treatment plan and alternative options are considered.
-
Biological Factors: Biological factors such as age and gender, genetic predisposition or imbalances in neurotransmitters like serotonin, dopamine, and norepinephrine can make individuals prone to treatment resistance.
-
Co-occurring Conditions: TRD may be influenced by co-occurring medical or psychiatric conditions such as cancer, heart disease, eating disorders, thyroid problems, anxiety disorders, and substance abuse (alcohol or drug abuse) that contribute to depression. these conditions can complicate the treatment process.
-
Psychosocial Factors: External factors such as chronic stress, trauma, or lack of social support that contribute to persistent depressive symptoms.
What Are the Symptoms of Treatment-Resistant Depression?
Symptoms of TRD include:
-
Persistent sadness.
-
Loss of interest or pleasure.
-
Sleep disturbances.
-
Appetite and weight changes.
-
Fatigue or lack of energy.
-
Feelings of worthlessness or guilt.
-
Restlessness or agitation.
-
Recurrent thoughts of death or suicide.
How Do Doctors Diagnose Treatment-Resistant Depression?
Doctors diagnose treatment-resistant depression when depression symptoms do not improve after trying at least two common antidepressants. These include SSRIs (selective serotonin reuptake inhibitors), SNRIs (serotonin and norepinephrine reuptake inhibitors), Bupropion, and Mirtazapine. Usually, one needs to take an antidepressant for about six to eight weeks to see if it helps.
If two antidepressants do not work, the doctor may send them to a psychiatrist. They will check the medical and mental health history, including:
-
All the medications they are taking, to see if any interfere with antidepressants or make depression worse.
-
Whether the patient is taking their medications (antidepressants) as prescribed.
-
Inquire about their experience with talk therapy or psychotherapy.
-
Physical health conditions like thyroid disease or chronic pain can affect depression.
-
Substance use issues.
-
Other mental health conditions that may better explain symptoms, like bipolar disorder or a personality disorder.
Based on this, the doctor may diagnose one with treatment-resistant depression and work with them to find a better treatment.
What Are the Treatment Strategies for Treatment-Resistant Depression?
There are five management strategies for treatment-resistant depression:
-
Optimization of antidepressants includes dose modification for a specific time and checking serum levels of antidepressants prescribed to determine whether they are supported by evidence-based data.
-
Switching of antidepressants is to change the ineffective antidepressant to a similar or different class of antidepressant such as SSRI to TCA, MAOI, and atypical antipsychotics with antidepressant properties.
-
Combination of antidepressants includes adding another antidepressant from other classes, such as tricyclic antidepressants (TCA) with selective serotonin reuptake inhibitors (SSRI), SSRI with monoamine oxidase inhibitors (MAOI), SSRI with Buspirone, etc.
-
Augmentation strategies include the addition of a second agent, which is not an antidepressant but may have antidepressant effects, such as thyroid hormones, lithium, pindolol, atypical antipsychotics, mood stabilizers, and dopamine agonists.
-
Somatic therapies, including VNS (vagus nerve stimulation), rTMS (repetitive transcranial magnetic stimulation), and DBS (deep brain stimulation) are most effective against TRD, seizures, and OCD (obsessive-compulsive disorder).
An integrated and adjunctive approach can be used to treat TRD by using antidepressants and managing side effects by increasing their efficacy with a combination of psychotherapy, lifestyle modifications, CAM (complementary and alternative medicine) strategies, and risk management strategies.
Other treatment options include:
-
Pharmacotherapy: The effect of antidepressants is compared with different classes for primary treatment, and a specific antidepressant is selected based on drug side effects, previous history of drug response, and cost of the medicine. The drugs used to treat depression are Tricyclic antidepressants (TCA), Moniamine oxidase inhibitors (MAOI), Selective serotonin reuptake inhibitors (SSRI), triiodothyronine (T3), and second-generation antidepressants group drugs.
-
Psychotherapy: Various psychotherapeutic treatments are used to treat depression, which includes CBT (cognitive behavior therapy), interpersonal psychotherapy, befriending, group psychoeducation, problem-solving therapy, psychodynamic psychotherapy, exercise, and cognitive behavior analysis. Psychotherapy alone can be helpful in treating mild to moderate depression, but a combination with pharmacotherapy has better outcomes in severe depression. Hence, it is considered to treat TRD as an adjunct to manage optimism and morale.
-
Electroconvulsive Therapy (ECT): ECT is a known treatment option to treat various mental disorders, including TRD, and is most effective with better responses. ECT is a first-line treatment option for severe TRD. ECT, along with pharmacotherapy, is efficient and prevents relapse.
-
Other Somatic Therapies: These are invasive therapies developed to prevent complications and side effects of ECT and are effective in TRD. this includes rTMS (repetitive transcranial magnetic stimulation) and VNS (vagus nerve stimulation) which are approved by the FDA (Food and Drug Administration) to treat TRD and interactable seizure disorders. Other therapies include magnetic seizure therapy and DBS (deep brain stimulation) for severe OCD (obsessive-compulsive disorder).
-
CAM Approach: Complementary and alternative medicine (CAM) approach refers to practices that are not considered standard medical care. This includes therapies such as acupuncture, massage, drinking green tea, tai chi, meditation, hypnosis, yoga, creative outlets, breathing exercises, vitamins, dietary supplements, and ayurvedic or naturopathic medicine. CAM strategies can help relieve anxiety, stress, and depression but are not approved by the FDA and should not be taken in large doses and without doctor consultation due to their harmful side effects.
Conclusion:
Most patients with major depression respond to antidepressant therapy, while some may need special treatment-resistant depression management strategies. Some individuals respond well to optimization and combined treatment strategies, and others to switching therapeutic options. The management strategies vary from person to person and individual needs. However, there is no specific treatment response or remission rate among the populations with TRD, and this poses a challenge for health professionals.
