10 Science-Based Solutions for Difficult-to-Treat Depression

People with treatment-resistant depression (that is, depression that is difficult to treat) often try various interventions in hopes of finding some relief. For example, some people have tried meditative practices such as mindfulness meditation. Some deep brain stimulation and similar neurostimulation treatments. Other psychedelic substances like psilocybin (magic mushrooms).

But are these interventions effective? What does the latest research show about safe and effective ways to manage symptoms of severe depression?

issued Published in October 2023 issue world psychiatryA recent paper by , RS McIntyre and colleagues discusses the diagnosis and evidence-based management of treatment-resistant depression.

Below is a summary of the article.

What is treatment-resistant depression?

According to the Food and Drug Administration (FDA), treatment-resistant depression requires: Failure to respond to two or more antidepressants.

However, many other definitions have been proposed. Most of these differ in the following ways:

• number of interventions (e.g., no response to one treatment, two, three or more treatments);
• The importance of baseline symptom severity.
• The importance of comorbidities (e.g. personality disorders).
• Intervention type (e.g., pharmacological enhancement, psychotherapy, electroconvulsive therapy).

More than 100 million people worldwide meet criteria for treatment-resistant depression, according to at least one definition.

Treatment-resistant depression is costly not only to individuals but also to society. This is associated with greater functional impairment, physical illness (e.g., heart disease, diabetes, obesity), absenteeism, need for disability benefits, health care utilization, caregiver burden, and interventions needed to manage it. associated with frequency and intensity.

Risk factor

Risk factors for treatment-resistant depression include:

• Low socio-economic status: Income and educational background are low.
• Adverse experience: History of life stress, childhood trauma or emotional abuse.
• Specific clinical factors: Higher baseline severity and duration, depression, anhedonia (i.e., inability to experience pleasure), anxiety, psychotic symptoms, comorbidities (metabolic syndrome, heart disease, diabetes, osteoporosis), cognitive impairment, especially attention. , working memory, processing speed impairments, and executive function.

Effective management of treatment-resistant depression

So what can be done to manage depression, which is difficult to treat?

Based on the available evidence, the following 10 strategies appear to be worth pursuing.

1. Extend antidepressant trials: Research shows that some patients who do not respond to antidepressants during the first 4 to 6 weeks may respond within 5 to 8 weeks and even 9 to 12 weeks.
2. switch antidepressants: If current medications are poorly tolerated, switching to an antidepressant, especially one with a different mechanism of action (e.g., from SSRIs to SNRIs or tricyclics), may be helpful.
3. Concomitant use of antidepressants: Using multiple drugs can reduce residual symptoms, as is the case with mirtazapine for insomnia. It can also help manage side effects, as is the case with bupropion for SSRI-induced sexual dysfunction.
4. IV Ketamine: Intravenous ketamine has been shown to not only reduce suicidal thoughts but also improve certain depressive symptoms more quickly than SSRIs.
5. Esketamine nasal spray: Esketamine is usually used in combination with antidepressants (but is not an antidepressant replacement). Like IV ketamine, esketamine is associated with rapid improvement in symptoms, particularly suicidality.Preliminary evidence suggests superiority over second-generation antipsychotics Quetiapine.
6. Second generation antipsychotics: Some evidence suggests that combining the antipsychotic drug olanzapine with the SSRI fluoxetine may have other effects. effective A treatment for depression that is difficult to treat.
7. Electroconvulsive therapy (ECT): ECT is one of the most effective interventions for managing treatment-resistant depression.Still it is underutilizedThis is partly due to tolerability concerns and barriers such as stigma and lack of skilled ECT physicians.
8. Repetitive transcranial magnetic stimulation (rTMS): Similar to ECT, rTMS is a neurostimulation therapy. Additionally, its new format (e.g. stanford neuromodulatory therapy), which are generally more acceptable to patients and have fewer side effects.according to 2022 The study found that “16 of 17 studies” found rTMS to be “effective, safe, and tolerable.”
9. vagus nerve stimulation: Vagus nerve stimulation is also an effective nerve stimulation therapy. It is approved by the FDA for the management of depression in patients who have not responded to at least four antidepressant trials.
10. psychotherapy: There is evidence to support the use of psychotherapy adjunctively, i.e. in combination with antidepressants. The most commonly studied therapies are interpersonal psychotherapy, cognitive behavioral therapy (CBT), and mindfulness-based cognitive therapy.

Concerns and risks

Potential problems associated with interventions for difficult-to-treat depression include:

• High costs and lack of availability: This is true for many new interventions such as vagus nerve stimulation.
• Drug-drug interactions: combine Antidepressants (SSRIs, tricyclics, MAOIs) increase the likelihood of side effects such as serotonin syndrome.
• Insufficient data on long-term use: For example, long-term data on the efficacy of rTMS and the safety and tolerability of IV ketamine (especially withdrawal effects and abuse potential) are needed.
• Side effects: For example, antipsychotics are associated with serious side effects such as metabolic syndrome (abdominal weight gain, high blood sugar, abnormal cholesterol) and extrapyramidal symptoms (muscle spasms, tremors, rigidity, restlessness).

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How to manage unresponsive depression Only Useful antidepressant strategies to date include trials of second-generation antipsychotics, rTMS, and adjunctive psychotherapy.

How to manage unresponsive depression multiple The authors recommend esketamine nasal spray, IV ketamine, adjuvant psychotherapy, ECT, and rTMS as antidepressants.

Meanwhile, many other treatments are under investigation. Some examples include S-adenosylmethionine, anti-inflammatory drugs (COX-2 inhibitors, statins, etc.), buspirone, dextromethorphan-bupropion combinations, lithium, L-methylfolate, thyroid hormones, and zuranolone.

Significant research has focused on psychedelics such as psilocybin, and for good reason. spare discovery.

This means that many effective treatments are available and many new treatments are being researched.

If you have depression that is difficult to treat

If you have treatment-resistant depression, talk to your doctor about the pros and cons of different interventions, including which antidepressants are best for you.

In the meantime, you can make healthy lifestyle changes to improve your physical and mental health. Therefore, try to get enough sleep, exercise regularly, eat a healthy diet, and use stress reduction techniques (deep breathing, yoga, meditation, relaxation training, etc.).

To find a therapist, visit: Psychology Today’s Therapy Directory.