What Treatments Help For Treatment Resistant Depression?

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Treatment resistant depression (TRD), also known as treatment refractory depression, is defined as failure to respond to 1st and 2nd line treatments. The first question to consider is if the diagnosis of major depressive disorder is correct. It may be a misdiagnosis, and may be the reason for the lack of response to treatment. For example, it could be a medical problem like hypothyroidism, electrolyte abnormalities, and anemia (B12 or iron deficiency), just to name a few. The depressive symptoms could also be caused by a medication or a substance of abuse. Once the medical problems are ruled out, then the psychiatric diagnosis may be incorrect. For example, if the diagnosis is adjustment disorder with depressed mood, then psychotropic medication may not alleviate the depressive symptoms…typically psychotherapy and addressing the stressor is helpful.

If indeed you have the right diagnosis of major depressive disorder, then the psychiatrist needs to consider if adequate dose and duration were tried with the previous treatments, and if not, to optimize the dose and duration. If symptoms continue after the optimization, then the psychiatrist may consider switching to a different class of antidepressant, such as switching from a selective serotonin reuptake inhibitor (ie sertraline- Zoloft) to a norepinephrine serotonin reuptake inhibitor (ie venlafaxine- Effexor). If this does not work, then the psychiatrist may consider augmenting the antidepressant with another medication such as lithium, thyroid hormone, or lamotrigine (Lamictal). Lamotrigine is a promising medication for TRD, and can even be used as monotherapy for TRD. Lamotrigine is advantageous for TRD in that it has a tolerable side effect profile when compared to other psychotropics for TRD like lithium. Lamotrigine just has to be dosed slowly to prevent severe rash from occurring.

Finally, electroconvulsive therapy (ECT), vagus nerve stimulation (VNS), and repetitive transcranial magnetic stimulation (rTMS) are last resort treatments for TRD. The most important aspect of TRD treatment is finding a psychiatrist who specializes in TRD and performs research in TRD. You can find these TRD-specialized psychiatrists at most university hospitals, as the university hospitals have all the infrastructure and expertise necessary to carry out the complex TRD treatments like ECT and VNS. rTMS is becoming more available in psychiatrists’ offices.

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Depressive Disorders

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Depressive disorders are characterized by low moods, feeling blue, or having apathy on exposure to a painful situation such as loss, disappointment, relationship problems, financial difficulties, and/or trauma. Bereavement, also known as grief, is differentiated from depression, in that bereavement is a normal reaction to the loss of a loved one and short-lived, whereas depression is more chronic, impacts your functioning, and lingers even with time passing. In addition to bereavement, sadness is a normal response to painful situations, where sadness is short-lived, while depression lingers and impacts your functioning. Both bereavement and sadness can turn into depression if the depressive symptoms linger past 2 weeks and you have multiple symptoms which impact your functioning.

Depression can occur when you are presented with a painful situation, and you start thinking negatively about the situation and about yourself. In response to the painful situation, you may think the situation is hopeless, you may think you are worthless, you may have no hope for the future, and/or you may think nothing will change. This negative thinking may then lead to feeling depressed. Depression may also be associated with other feelings, like shame, guilt, anger, or anxiety. Your self-esteem may also be low, you may not find pleasure in things, you may have difficulty concentrating, and you may have no hope for the future, to the point where you may also have thoughts of suicide. In addition to feeling low moods, you may have physical sensations of depression, including fatigue, exhaustion, lethargy, sleep disturbance, appetite changes, body pains, and headaches. Because you are depressed from the negative thinking and have fatigue, sleep problems, pain and eating problems, you tend to do less and less. Soon, you start to isolate and stop doing the things that used to bring you pleasure. You may also stop going to work, stay in bed, and ignore your relationships. These isolating behaviors in turn make you feel more depressed, getting you caught up in a vicious cycle of depression.

Depression, also called major depressive disorder, occurs when the depressive symptoms cause impairment of your functioning in relationships and work/school. The major depressive disorders include major depressive disorder, dysthymic disorder, and bipolar depression. Other depressive disorders include substance induced mood disorder, mood disorder due to a general medical condition, adjustment disorder with depression, minor depressive disorder, recurrent brief depressive disorder, and premenstrual dysphoric disorder. The major disorders are associated with the following:

  • Major depressive disorder- low moods or anhedonia with other symptoms of depression for at least 2 weeks
  • Dysthymic disorder- chronic depression for at least 2 years
  • Bipolar depression- depression that occurs in bipolar disorder

Depression treatment involves psychotherapy, with cognitive behavioral therapy (CBT) having the most evidence for efficacy. CBT works on the premise that events or situations do not directly cause the depression; rather, the thoughts we have or the meaning we give the events causes the depression. CBT works by identifying the maladaptive thoughts, working on more adaptive thoughts, and suppressing/distancing oneself from the maladaptive thinking. In addition, CBT addresses the avoidant and isolative behaviors which serve to sustain the depression over the long term. Other forms of psychotherapy include depth or insight oriented psychotherapy, which addresses the causes and the proximal determinants of the depression. If psychotherapy is not effective, or if the depressive symptoms are severe, then pharmacotherapy with depression medications can be considered after a psychiatric assessment. Other treatments for depression include self-help treatments, natural supplements, and alternative interventions for depression like exercise, meditation, and diet. If you are experiencing severe depressive symptoms or have suicidal thoughts, please contact your doctor immediately.

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