Major Depressive Disorder: Much More Than Sadness

Major Depressive Disorder (MDD) is much more than a mere feeling of sadness, which nearly everyone experiences from time to time.  The symptoms, as we will develop later on, linger for at least 2 consecutive weeks. MDD is a serious disorder which is associated with increased mortality, as people with anxiety/depression in the US die 7.9 years earlier than the general population [1].

According to a study done in 2006, the proportion of the Lebanese population that was affected by major depression during a 12-month period was 4.9% [2]

What is Major Depressive Disorder?

According to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V), which is a reference used by medical professionals to define mental diseases, the diagnosis of MDD is based on the presence of 5 or more of the following symptoms, nearly every day, for at least 2 consecutive weeks: (with at least 1 of the first 2 which are cardinal symptoms)

• Depressed mood
• Loss of interest or pleasure in all, or almost all, usual activities
• Significant weight loss or weight gain
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Feelings of worthlessness or excessive or inappropriate guilt
• Diminished ability to think or concentrate or indecisiveness
• Recurrent thoughts of death or suicide.

Also, these symptoms must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning

A great definition for MDD would be: a malady of stress adaptation in the brain or a disorder of stress response & adaptation (Neuroplasticity) [3].

Neuroplasticity is defined as the ability of the brain to modulate its connections in order to better deal with stressors

Interestingly enough, research showed that psychotherapy, which is the first line treatment for depression, as well as pharmacological treatments, act by providing the brain with better neuroplasticity in order to deal with outside stressors in more effective ways.

Diagnosis:

A primary care physician or a psychotherapist can usually diagnose depression by asking questions about medical history and symptoms.

Many people with depression do not seek diagnosis or treatment because of society’s attitudes concerning mental health

Actually, according to the national institute of mental health, it takes the average person suffering with a mental illness over 10 years to ask for help. The sufferers may blame themselves for their depression or may worry about what others will think.

For that reason, family members or friends need to encourage suspected depression-sufferers to seek help

There are still no specific medical tests to diagnose depression, so it is diagnosed according to the DSM-V criteria. However, it is important to be evaluated by a primary care physician to make sure that the symptoms are not due to a medical condition or medication.  It is also crucial to rule out any co-occurring mania or hypomania, which  would warrant a diagnosis of bipolar disorder instead of Major Depressive Disorder.

Etiology and Risk factors:

Many genes have been associated with MDD. An example would be the Serotonin Transporter SERT gene [4]. One study suggested that people who carry the “short” allele of this gene have a two-fold increased risk of developing MDD after 4 major stressing life events compared to people with the “long” allele.  

This study, as well as more than 54 replications in the literature, highly suggest that the cause of MDD is mainly an interplay between many genes, such as SERT, as well as external factors like lifestyle and stressors.

Expected Duration:

Major depressive episodes vary in length; however, untreated episodes of MDD last on average many months. In addition to that, symptoms can vary in intensity during the same episode.

If not treated, depression can become long-lasting

Furthermore, there is a positive correlation between the number of major depressive episodes faced and the probability of recurrence [5]. Treatment can shorten the duration and intensity of a depressive episode.

Treatment: [6]

The best initial treatment would be a combination of psychotherapy (Cognitive Behavioral Therapy) and medication. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed first, and they include fluoxetine, citalopram, escitalopram, sertraline and paroxetine. They are the safest compared with other antidepressants.

We must note that, no medication is generally completely safe from side effects, and medications, when prescribed by a professional, offer much more benefit compared to living with this serious medical condition.

SSRIs are known to cause problems with sexual functioning and increased anxiety in the early stages of treatment. SSRIs usually take up to 2 months in order to reach their desired effect.

Other effective antidepressants include bupropion, and Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) such as duloxetine and venlafaxine. Mirtazapine is especially useful when dealing with lack of appetite along with depression. Older classes of antidepressants, such as monoamine oxidase inhibitors and tricyclic antidepressants, can still be used. They are efficient and can be very useful in treatment-resistant depression.

It may take several trials in order to tailor a treatment regimen that suits the patient best

Once the right medication is found, it may take up to a few months to find a proper dose and for the optimal positive effect to be seen.

In some situations where other treatment options yield no result and if the patient is acutely suicidal, a treatment called electroconvulsive therapy (ECT) can be a life-saving option. This treatment is controversial, but very effective. In ECT, an electrical impulse is applied to the person’s scalp and passes to the brain, causing a controlled seizure. The patient is under anesthesia and is monitored carefully. Medication is given before the procedure to prevent injury resulting from outward signs of convulsion. Improvement is seen gradually over a period of time. ECT acts rapidly and is the most effective treatment for some very severe forms of depression.

Prognosis:

Treatment of depression has become more sophisticated and effective and the prognosis with treatment is excellent. The intensity of symptoms and the frequency of episodes are often significantly reduced and many people recover completely.

When treatment is successful, it is important to stay in close touch with your healthcare provider or therapist, because maintenance treatment is often required to prevent depression from returning.  Just like other chronic diseases, like diabetes or hypertension, major depressive disorder, being also a physical illness, should be considered as such and treated accordingly.

References:

1- Pratt L, Druss B, Manderscheid R, Walker E. Excess mortality due to depression and anxiety in the United States: results from a nationally representative survey. General Hospital Psychiatry. 2016;39:39-45.

2- Karam E, Mneimneh Z, Karam A, Fayyad J, Nasser S, Chatterji S et al. Prevalence and treatment of mental disorders in Lebanon: a national epidemiological survey. The Lancet. 2006;367(9515):1000-1006.

3- Duman R. A Molecular and Cellular Theory of Depression. Archives of General Psychiatry. 1997;54(7):597.

4- Caspi A. Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene. Science. 2003;301(5631):386-389.

5- Keller M, Boland R. Implications of failing to achieve successful long-term maintenance treatment of recurrent unipolar major depression. Biological Psychiatry. 1998;44(5):348-360.

6- Publishing H. Major Depression – Harvard Health [Internet]. Harvard Health. 2021 [cited 26 March 2021]. Available [here]