Depression; Causes, Symptoms, Diagnosis, Treatment

Depression

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Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest. Also called major depressive disorder or clinical depression, it affects how you feel, think and behave and can lead to a variety of emotional and physical problems. Depression is a serious medical illness. Also called “major depressive disorder,” or “unipolar depression,” it affects about 350 million people worldwide and is a leading cause of disability, according to the World Health Organization.

Pathophysiology

The underlying pathophysiology of major depressive disorder has not been clearly defined. Current evidence points to a complex interaction between neurotransmitter availability and receptor regulation and sensitivity underlying the affective symptoms.

  • Clinical and preclinical trials suggest a disturbance in central nervous system serotonin (5-HT) activity as an important factor. Other neurotransmitters implicated include norepinephrine (NE), dopamine (DA), glutamate, and brain-derived neurotrophic factor (BDNF).[7]
  • The role of CNS 5-HT activity in the pathophysiology of major depressive disorder is suggested by the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs). Research findings imply a role for neuronal receptor regulation, intracellular signaling, and gene expression over time, in addition to enhanced neurotransmitter availability.
  • The seasonal affective disorder is a form of the major depressive disorder that typically arises during the fall and winter and resolves during the spring and summer. Studies suggest that seasonal affective disorder is also mediated by alterations in CNS levels of 5-HT and appears to be triggered by alterations in circadian rhythm and sunlight exposure.
  • Vascular lesions may contribute to depression by disrupting the neural networks involved in emotion regulation—in particular, frontostriatal pathways that link the dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate, and dorsal cingulate. Other components of limbic circuitry, in particular, the hippocampus and amygdala, have been implicated in depression.

Types of Depression

Depressive Disorders Other Than Major Depression That May Benefit From Exercise Programs
Types of Depression Definition
  • Dysthymia
Dysthymia is a mild but long-term form of depression. Symptoms usually last for at least two years.
  • Atypical depression
This type involves only some of the symptoms of major depression. Common symptoms of atypical depression include increased appetite or weight gain, sleepiness or excessive sleep, and feeling extremely sensitive to rejection.
  • Seasonal depression
Seasonal depression, also known as winter depression or blues, summer depression or blues, was considered a mood disorder in which people who have normal mental health throughout most of the year, experience depressive symptoms in the winter or summer.
  • Bipolar depression
Bipolar disorder (manic-depressive disorder) is diagnosed in individuals experiencing episodes of a frenzied mood known as mania, typically alternating with episodes of depression.
  • Postnatal depression
Postnatal depression or Postpartum depression is a type of clinical depression which can affect women, and less frequently men, typically after childbirth. It usually develops in the first four to six weeks after childbirth, even may develop after several months. However many women are not aware they have the condition. Common symptoms are low mood, feeling unable to cope and difficulty sleeping.
  • Premenstrual syndrome
Premenstrual syndrome is a collection of emotional symptoms, with or without physical symptoms, related to a woman’s menstrual cycle.

Major Depression

You may hear your doctor call this “major depressive disorder.” You might have this type if you feel depressed most of the time for most days of the week.

Some other symptoms you might have are:

  • Loss of interest or pleasure in your activities
  • Weight loss or gain
  • Trouble getting to sleep or feeling sleepy during the day
  • Feelings restless and agitated, or else very sluggish and slowed down physically or mentally
  • Being tired and without energy
  • Feeling worthless or guilty
  • Trouble concentrating or making decisions
  • Thoughts of suicide
  • Electroconvulsive therapy (ECT)
  • Repetitive transcranial magnetic stimulation (rTMS)

ECT uses electrical pulses and rTMS uses a special kind of magnet to stimulate certain areas of brain activity. This helps the parts of your brain that control your mood work better.

Persistent Depressive Disorder

If you have depression that lasts for 2 years or longer, it’s called persistent depressive disorder. This term is used to describe two conditions previously known as dysthymia (low-grade persistent depression) and chronic major depression.

You may have symptoms such as

  • Change in your appetite (not eating enough or overeating)
  • Sleep too much or too little
  • Lack of energy, or fatigue
  • Low self-esteem
  • Trouble concentrating or making decisions
  • Feel hopeless

Bipolar Disorder

Someone with bipolar disorder, which is also sometimes called “manic depression,” has mood episodes that range from extremes of high energy with an “up” mood to low “depressive” periods.

When you’re in the low phase, you’ll have the symptoms of major depression. Medication can help bring your mood swings under control. Whether you’re in a high or a low period, your doctor may suggest a mood stabilizer, such as lithium.

The FDA has approved three medicines to treat the depressed phase

  • Seroquel
  • Latuda
  • Olanzapine-fluoxetine combination

Seasonal Affective Disorder (SAD)

The seasonal affective disorder is a period of major depression that most often happens during the winter months, when the days grow short and you get less and less sunlight. It typically goes away in the spring and summer.

If you have SAD, antidepressants can help. So can light therapy. You’ll need to sit in front of a special bright light box for about 15-30 minutes each day.

Psychotic Depression

People with psychotic depression have the symptoms of major depression along with “psychotic” symptoms, such as:

  • Hallucinations (seeing or hearing things that aren’t there)
  • Delusions (false beliefs)
  • Paranoia (wrongly believing that others are trying to harm you)

Peripartum (Postpartum) Depression

Women who have major depression in the weeks and months after childbirth may have peripartum depression. Antidepressant drugs can help similarly to treating major depression that is unrelated to childbirth.

Premenstrual Dysphoric Disorder (PMDD)

Women with PMDD have depression and other symptoms at the start of their period.

Besides feeling depressed, you may also have:

  • Mood swings
  • Irritability
  • Anxiety
  • Trouble concentrating
  • Fatigue
  • Change in appetite or sleep habits
  • Feelings of being overwhelmed

‘Situational’ Depression

This isn’t a technical term in psychiatry. But you can have a depressed mood when you’re having trouble managing a stressful event in your life, such as a death in your family, a divorce, or losing your job. Your doctor may call this “stress response syndrome.”

Psychotherapy can often help you get through a period of depression that’s related to a stressful situation.

Atypical Depression

This type is different than the persistent sadness of typical depression. It is considered to be a “specifier” that describes a pattern of depressive symptoms. If you have atypical depression, a positive event can temporarily improve your mood.

Other symptoms of atypical depression include:

  • Increased appetite
  • Sleeping more than usual
  • Feeling of heaviness in your arms and legs
  • Oversensitive to criticism

Antidepressants can help. Your doctor may suggest a type called an SSRI (selective serotonin reuptake inhibitor) as the first-line treatment.

Causes of Depression

There are a number of factors that may increase the chance of depression, including the following:

  • Genetics  – A family history of depression may increase the risk. People have an increased risk of depression if other people in their family have had depression. It’s thought that depression is a complex trait, meaning that there are probably many different genes that each exert small effects, rather than a single gene that contributes to disease risk. The genetics of depression, like most psychiatric disorders, are not as simple or straightforward as in purely genetic diseases such as Huntington’s chorea or cystic fibrosis.
  • Abuse – Past physical, sexual, or emotional abuse can increase the vulnerability to clinical depression later in life.
  • Certain medications – Some drugs, such as isotretinoin (used to treat acne), the antiviral drug interferon-alpha, and corticosteroids, can increase your risk of depression.
  • Conflict – Depression in someone who has the biological vulnerability to develop depression may result from personal conflicts or disputes with family members or friends.
  • Death or a loss – Sadness or grief from the death or loss of a loved one, though natural, may increase the risk of depression.
  • Major events – Even good events such as starting a new job, graduating, or getting married can lead to depression. So can moving, losing a job or income, getting divorced, or retiring. However, the syndrome of clinical depression is never just a “normal” response to stressful life events.
  • Other personal problems – Problems such as social isolation due to other mental illnesses or being cast out of a family or social group can contribute to the risk of developing clinical depression.
  • Serious illnesses – Sometimes depression co-exists with a major illness or may be triggered by another medical condition.
  • Substance abuse – Nearly 30% of people with substance abuse problems also have major or clinical depression.
  • Traumatic childhood experiences –  such as abuse and neglect
  • Chronic anxiety disorders – in childhood and puberty  combined with low self-esteem and insecurity
  • Biochemical changes – The metabolism in the brain has been found to be different in people with depression, and nerve impulses travel more slowly Certain chemical messengers and hormonal changes can also play a role
  • Personality traits –  such as a lack of self-confidence
  • Dependence on alcohol, tablets or drugs –  This is sometimes a consequence of depression, but it might also be one thing that leads to depression or could make it worse
  • Physical medical problems – such as strokes, heart attacks, cancer or an underactive thyroid.
  • Lack of light –  The dark fall and winter months can lead to depression in some people
  • Taking particular medications
  • Distressing events such as the death of a loved one or the end of a relationship
  • Long-term stress and feeling like you can’t cope or feeling under-challenged
  • Loneliness

 Drugs That Might Cause Depression (Excessive Elation)

  • The following drugs could cause symptoms of depression. Even though the risk for some of these drugs might not be high, you should discuss the risk with your doctor if you take them:
  • Corticosteroids. This group of drugs decreases inflammation (swelling) and reduces the activity of the immune system (cells that fight infection). Examples include Azmacort, Flovent, hydrocortisone, prednisone, and triamcinolone.
  • Cyclosporine. This drug is used to suppress the immune system to prevent the rejection of transplanted organs.
  • Carbidopa/levodopa (Duopa, Parcopa, Sinemet). These medicines treat Parkinson’s disease.
  • Baclofen intrathecal (Lioresal). This is a muscle relaxant and antispastic agent. It’s often used to treat multiple sclerosis and spinal cord injuries.
  • All antidepressants, including MAOIs (monoamine oxidase inhibitors, such as phenelzine (Nardil) or tranylcypromine (Parnate); SSRIs (selective serotonin reuptake inhibitors such as escitalopram (Lexapro), fluoxetine (Prozac), and paroxetine (Paxil); SNRIs (serotonin/norepinephrine reuptake inhibitors, such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), levomilnacipran (Fetzima), venlafaxine (Effexor XR); and tricyclic antidepressants (such as nontriptyline (Pamelor).
  • Methylphenidate (Ritalin) or amphetamine. These are stimulant drugs used to treat attention deficit hyperactivity disorder (ADHD).
  • Levothyroxine (Synthroid). This drug is commonly prescribed as a thyroid hormone replacement.
  • Certain antibiotics, such as ciproflozacin and gentamicin
  • Antimalarial drugs, such as chloroquine and mefloquine
  • Antineoplastic drugs such as 5-fluorouracil and ifosfamide

Symptom of Depression

People who have depression fall into an emotional black hole for weeks or months, and often can’t see any way out. Different people experience depression differently: Some mainly feel sad and down. Everything seems pointless. Nothing and nobody can lift their spirits. Others aren’t sad, but instead feel empty inside, exhausted and emotionally numb. And others may suffer from agonizing worries, fears, and anxiety. Typical signs of depression include:

  • Feeling down all the time
  • Loss of energy and motivation, exhaustion
  • Lack of joy and interest, even in things and hobbies that used to be enjoyable
  • Low self-esteem and low self-confidence
  • Feeling guilty and constantly brooding over things
  • Difficulties concentrating and making decisions
  • Apathy and emotional numbness
  • Withdrawing from friends and family
  • Hopelessness and worrying about the future
  • Not wanting to live anymore, or suicidal thoughts

Physical symptoms that are sometimes associated with  include:

  • Tiredness
  • Sleep problems
  • Loss of appetite
  • Weight loss or gain
  • Loss of sexual desire
  • Digestion problems, such as constipation
  • Increased sensitivity to pain

Physical symptoms like these are particularly common in older people. Depression can arise at any age, in various phases of life and under various circumstances. These things influence the symptoms of depression and – sometimes – the way people and those around them experience depression too. For example, in older people, depression is often wrongly interpreted as a sign of old age or dementia.

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Depression symptoms can vary from mild to severe and can include:

  • Feeling sad or having a depressed mood
  • Loss of interest or pleasure in activities once enjoyed
  • Changes in appetite — weight loss or gain unrelated to dieting
  • Trouble sleeping or sleeping too much
  • Loss of energy or increased fatigue
  • Increase in purposeless physical activity (e.g., hand-wringing or pacing) or slowed movements and speech (actions observable by others)
  • Feeling worthless or guilty
  • Difficulty thinking, concentrating or making decisions
  • Thoughts of death or suicide
  • loss of interest or pleasure in almost all activities
  • changes in appetite or weight
  • disturbed sleep or sleeping too much
  • slowed or restless movements
  • fatigue or loss of energy
  • feelings of worthlessness or excessive guilt
  • trouble in thinking, concentrating, or making decisions
  • thoughts of death or suicide

Symptoms must last at least two weeks for a diagnosis of depression.

Diagnosis of Depression 

These are the nine symptoms listed in the DSM V and five of these  must be present to make the diagnosis (one of the symptoms should be depressed mood or loss of interest or pleasure):

  • Sleep disturbance,
  • Interest/pleasure reduction
  • Guilt feelings or thoughts of worthlessness.
  • Energy changes/fatigue
  • Concentration/attention impairment.
  • Appetite/weight changes.
  • Psychomotor disturbances.
  • Suicidal thoughts, and
  • Depressed mood.

All patients with depression should be evaluated for suicidal risk. Any suicide risk must be given prompt attention which could include hospitalization or close and frequent monitoring.

Other areas of investigation include:

  • Past medical history and family medical history, and current medications.
  • Social history with a focus on stressors and the use of drugs and alcohol.
  • History and physical examination to rule out organic causes of depression. Depressive symptoms and their severity are also evaluated with the help of questionnaires such as the Beck’s Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), and Zung Self Rating Depression Scale.

Evaluation

The diagnosis of depression is based on history and physical findings. No diagnostic laboratory tests are available to diagnose a major depressive disorder. Laboratory studies are, however, useful to exclude medical illnesses that may present as major depressive disorder. These laboratory studies might include the following:

  • Complete blood cell (CBC) count
  • Thyroid-stimulating hormone (TSH)
  • Vitamin B-12
  • Rapid plasma reagin (RPR)
  • HIV test
  • Electrolytes, including calcium, phosphate, and magnesium levels
  • Blood urea nitrogen (BUN) and creatinine
  • Liver function tests (LFTs)
  • Blood alcohol level
  • Blood and urine toxicology screen
  • Arterial blood gas (ABG)
  • Dexamethasone suppression test (Cushing disease, but also positive in depression)
  • Cosyntropin (ACTH) stimulation test (Addison disease)
  • Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain should be considered if organic brain syndrome or hypopituitarism is included in the differential diagnosis.

There are a number of online tools and self-tests to determine whether you may be depressed and need to seek help, but only your doctor can diagnose clinical depression.

According to the American Psychiatric Association, you must meet specific criteria to be clinically diagnosed with major depression.

You must have experienced at least five of the following nine symptoms for at least two weeks, and these symptoms must have significantly impaired your ability to function in your daily life:

  • Feeling sad or having a depressed mood for most of the day
  • Loss of interest or pleasure in once-enjoyable activities
  • Unexplained weight loss or gain
  • Insomnia or sleeping too much
  • Fatigue or loss of energy
  • Restlessness or slowed movements, speech, and thoughts
  • Feelings of worthlessness and guilt
  • Difficulty thinking, concentrating or making decisions
  • Thoughts of death or suicide

Other forms of depression have other specific diagnostic criteria.

Doctors should also screen you for bipolar disorder, a brain disorder that causes unusual shifts in mood, energy, and activity levels, as well as changes in your ability to do everyday tasks. If certain medications approved for treatment of depression are wrongly prescribed to a person with bipolar disorder, they can cause mania, a type of unusually elevated or excited mood. If mania is severe, a person can become psychotic.

Treatment with Medication

Not all depression requires treatment with medication. But medications approved for the treatment of depression by the U.S. Food and Drug Administration.

Antidepressants are medications that are thought to work by changing brain chemicals called neurotransmitters—primarily serotonin, norepinephrine, and dopamine—which are involved in regulating mood.

Some antidepressants have classifications

Electroconvulsive therapy is useful for patients who are not responding well to medications or are suicidal.

Medications used for the treatment of depression include the following

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin/norepinephrine reuptake inhibitors (SNRIs)
  • Atypical antidepressants
  • Serotonin-Dopamine Activity Modulators (SDAMs)
  • Tricyclic antidepressants (TCAs)
  • Monoamine oxidase inhibitors (MAOIs)
  • Selective serotonin reuptake inhibitors (SSRIs) – SSRIs have the advantage of ease of dosing and low toxicity in overdose. They are also the first-line medications for late-onset depression.
  • SSRIs include the following – Citalopram (Celexa); Escitalopram (Lexapro); Fluoxetine (Prozac);  Fluvoxamine (Luvox); Paroxetine (Paxil) Sertraline (Zoloft); Vilazodone (Viibryd); Vortioxetine (Brintellix)
  • Serotonin/norepinephrine reuptake inhibitors (SNRIs) – SNRIs, which include venlafaxine (Effexor), desvenlafaxine (Pristiq), duloxetine (Cymbalta), and levomilnacipran (Fetzima) can be used as first-line agents, particularly in patients with significant fatigue or pain syndromes associated with the episode of depression. SNRIs also have an important role as second-line agents in patients who have not responded to SSRIs.
  • Atypical antidepressants – Atypical antidepressants include bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone, and trazodone (Desyrel). They have all been found to be effective in monotherapy in major depressive disorder and may be used in combination therapy for more difficult to treat depression.
  • Serotonin-Dopamine Activity Modulators (SDAMs) –  SDAMs include brexpiprazole (Rexulti) and aripiprazole (Abilify). SDAMs act as a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and as an antagonist at 5-HT2A and noradrenaline alp Brexpiprazole is indicated as adjunctive therapy for major depressive disorder (MDD).
  • Tricyclic antidepressants (TCAS) – TCAs include the following: Amitriptyline (Elavil); Clomipramine (Anafranil); Desipramine (Norpramin); Doxepin (Sinequan); Imipramine (Tofranil); Nortriptyline (Pamelor); Protriptyline (Vivactil); Trimipramine (Surmontil). TCAs have a long record of efficacy in the treatment of depression. They are used less commonly because of their side-effect profile and their considerable toxicity in overdose.
  • Monoamine oxidase inhibitors (MAOIs) –  MAOIs include isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Emsam), and tranylcypromine (Parnate). These agents are widely effective in a broad range of effective and anxiety disorders. Because of the risk of hypertensive crisis, patients on these medications must follow a low-tyramine diet. Other adverse effects can include insomnia, anxiety, orthostasis, weight gain, and sexual dysfunction.
  • Psychotherapy – Cognitive Behavior Therapy and Interpersonal Therapy are evidence-based psychotherapies that have been found to be effective in the treatment of depression.
  • Cognitive-behavioral therapy (CBT) – CBT is a structured, and didactic form of therapy that focuses on helping individuals identify and modify maladaptive thinking and behavior patterns (16 to 20 sessions). It is based on the premise that patients who are depressed exhibit the “cognitive triad” of depression, which includes a negative view of themselves, the world, and the future. Patients with depression also exhibit cognitive distortions that help to maintain their negative beliefs. CBT for depression typically includes behavioral strategies (i.e., activity scheduling), as well as cognitive restructuring for the purpose of changing negative automatic thoughts and addressing maladaptive schemas.
  • Mindfulness-based cognitive therapy (MBCT)  – was designed to reduce relapse among individuals who have been successfully treated for an episode of recurrent major depressive disorder. The primary treatment component is mindfulness training. MBCT specifically focuses on ruminative thought processes as being a risk factor for relapse. Research indicates that MBCT is effective in reducing risk of relapse in patients with recurrent depression, especially in those with the most severe residual symptoms. Interpersonal therapy (IPT)
  • Interpersonal Therapy (IPT) – Interpersonal therapy (IPT) is a time-limited (typically 16 sessions) treatment for major depressive disorder. IPT draws from attachment theory and emphasizes the role of interpersonal relationships, focusing on current interpersonal difficulties. Specific areas of emphasis include grief, interpersonal disputes, role transitions, and interpersonal deficits. Some evidence shows that the most effective way to treat many patients with depression is through both talk therapy and prescribed antidepressant medication,” adds Mitchell Mathis, M.D., director of the Division of Psychiatry Products at the FDA. Talk to your doctor about the best treatment for you.
  • Electroconvulsive Therapy (ECT) – ECT is a highly effective treatment for depression. The onset of action may be more rapid than that of drug treatments, with benefit often seen within 1 week of commencing treatment. A course of ECT (usually up to 12 sessions) is the treatment of choice for patients who do not respond to drug therapy, are psychotic, or are suicidal or dangerous to themselves. Thus, the indications for the use of ECT include the following:
  • Need for a rapid antidepressant response  Failure of drug therapies
  • History of good response to ECT
  • Patient preference
  • High risk of suicide
  • High risk of medical morbidity and mortality

Although advances in brief anesthesia and neuromuscular paralysis have improved the safety and tolerability of ECT, this modality poses numerous risks, including those associated with general anesthesia, postictal confusion, and, more rarely, short-term memory difficulties.

  • Thyroid hormones – are useful in euthyroid patients for converting nonresponders into responders. It has been assumed that tri-iodothyronine (T3) would be preferentially indicated in unipolar patients (a 25-μg to 37.5-μg daily dose accelerates the time of response to antidepressants), while thyroxine (T4) combined with lithium would be useful in the prevention of mood episodes in bipolar patients (however the daily dose is generally high, about 200 to 400 μg, and this may lead to possible adverse effects [thyrotoxicosis]).
  • Dopamine agonists – such as bromocriptine, pergolide, pramipexole, and ropinirole have been used with promising results as an adjuvant to antidepressants especially in bipolar patients. These agonists are also useful in depressed patients with Parkinson’s disease and in patients with restless legs syndrome.
  • Atypical antipsychotics – such as risperidone, olanzapine, and aripiprazole may also be useful as an adjunctive medication in nonpsychotic treatment-resistant patients. Psychostimulants such as d-amphetamine, methylphenidate, and modafinil added to antidepressants have also been found to be effective in resistant depression.
  • Electroconvulsive therapy (ECT) – remains an option for resistant depression, although there is only a weak possibility that a given patient will respond to ECT if he or she has previously failed to respond to pharmacotherapy
  • Transcranial magnetic stimulation – (which involves the depolarization of neurons in a localized area of the brain by applying a powerful magnetic field in rapid flux), vagus nerve stimulation and deep brain stimulation have been proposed as alternatives to ECT. The efficacy of these approaches is promising but needs further confirmation.
  • Chronotherapeutics – such as wake therapy- single or repeated sleep deprivation, total (all night) or partial (second half of the night) – and light therapy have been proposed as an adjuvant to conventional antidepressants in unipolar patients, or lithium in bipolar patients.
  • Antiglucocorticoid treatments  have been proposed, assuming that cortisol-lowering treatments may be of clinical benefit in patients refractory to traditional antidepressants.
  • Ketoconazole  which inhibits Cortisol biosynthesis, and acts at the receptor level as a glucocorticoid antagonist, has led to mixed results: some authors have found antidepressant properties, while others, despite the inhibition of Cortisol, found only a weak impact on depression. Moreover, the numerous side effects of ketoconazole (including hepatotoxicity) mandate frequent laboratory monitoring.
  • Mifepristone (RU-486) – a potent glucocorticoid and progesterone receptor antagonist, may be effective in the treatment of psychotic and bipolar depression and may re-regulate the HPA axis. CRH1 receptor antagonists have therapeutic potential in disorders that involve excessive CRH activity and some are currently under investigation as antidepressants
Specific depression subscales derived from the HAM-D by the microanalytic approach. SRI, Serotonin reuptake inhibitor; NRI, Noradrenaline reuptake inhibitor; DRI, Dopamine reuptake inhibitor; MAOI, monoamine oxidase inhibitor
1. ANTIDEPRESSANT DRUGS
Tricyclic and tetracyclic antidepressants (TCAs)
  • clomipramine (SRI>>NRI); amitriptyline (SRI>NRI)
  • imipramine,
  • doxepin
  • amoxapine (NRI=SRI)
  • desipramine (NRI>SRI))
  • maprotiline (NRI)
Selective serotonin reuptake Inhibitors (SSRIs)
  • citalopram, escitalopram
  • fluoxetine (also NRI, and weak D7 receptor blocker)
  • fluvoxamine (also weak NRI, and melatonin agonist)
  • paroxetine (also NRI>>DaRI)
  • sertraline (also DaRI>>NRI)
Selective serontonin and noradrenaline reuptake
inhibitors (SNRIs)
  • venlafaxine, milnacipran, duloxetine
Noradrenaline α2 receptor antagonist and serotonin 5-HT2
receptor antagonist
  • mianserine, mirtazapine
Serotonin (5-HT2) receptor antagonists
  • trazodone, nefazodone
Noradrenaline reuptake inhibitor
  • reboxetine
Dopamine reuptake inhibitors
  • bupropion (also weak NI), methylphenidate
Monoamine oxidase inhibitors(MAOIs)
  • irreversible and nonselective: iproniazide
  • reversible and selective:
  • MAOI-A (moclobemide, toloxatone)
  • MAOI-B (selegiline)
Melatoninergic (MT1/2) receptor agonist and selective
5-HT2 receptor antagonist
  • agomelatine
Others
  • Tianeptine
  • herbal medicine – hypericum perforatum (St. John’s wort)
  • amino acid derivative S-adenosylmethionine (SAM-e)
  • tryptophan and 5 hydroxytryptophan dietary supplements
MOOD STABILIZERS
Lithium salts
Antiepileptics
  • carbamazepine/oxcarbazepine, sodium valproate/divalproate/
  • iopromide, lamotrigine
NONCHEMICAL” THERAPIES
Sleep deprivation (total: all night; partial: second half
of the night)
  • Light therapy
  • Electroconvulsive therapy
  • Magnetic stimulation
  • Vagus nerve stimulation
  • Deep brain stimulation
PSYCHOTHERAPY
  • Cognitive therapy
  • interpersonal psychotherapy
  • Problem-solving therapy
  • Psychodynamic-interpersonal psychotherapy
  • Psychoanalytic oriented psychotherapy
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Antidepressant Effectiveness

In general, you must take regular doses of a prescribed antidepressant for several weeks before you’re likely to have the medication’s full effect.

You shouldn’t stop taking medication without talking with your doctor—even if you feel better. Stopping can result in withdrawal symptoms like anxiety and irritability. Or depression could return.

Note: A significant percentage of people may not respond to a prescribed antidepressant. In these cases, switching to a different medication or adding another medication can sometimes help treat symptoms. Some people may not respond to medication at all, Mathis notes. If you have concerns about antidepressants you are taking, talk with your doctor.

Common Side Effects of Depression

Common side effects of antidepressants can include:

  • Nausea and vomiting
  • Weight gain
  • Diarrhea
  • Sleep disturbances
  • Sexual problems

It may take some time for your doctor to determine the medication that works best for you.

Serious Risks of Depression

Some antidepressants can have serious risks. Discuss these risks with your doctor. Some of the relevant risks are listed below.

Suicidal thinking – In 2004, the FDA asked manufacturers to add a boxed warning to the labeling of all antidepressant medications. This labeling warns about the increased risk of suicidal thinking or suicidal behavior in children and adolescents taking antidepressants during initial treatment and with dose increases. In 2007, FDA requested that the warning be extended to include young adults through age 24.

If you or someone you know is having thoughts of suicide, you can immediately call your doctor; go to a hospital emergency room.

Birth defects – Some antidepressant medications might harm a fetus if taken during pregnancy. If you are considering an antidepressant medication and are pregnant, plan to become pregnant, or breastfeeding, talk to your doctor about benefits and risks.

High blood pressure – Those taking monoamine oxidase inhibitors must avoid certain foods that contain high levels of the chemical tyramine. This chemical is in many kinds of cheese, wines and pickles, and some medications including decongestants. If you take MAOIs and consume this chemical, they may interact and cause a sharp increase in blood pressure, which could lead to a stroke or other complications. Talk to your doctor about the best diet for you.

Home Remedies for Depression

Exercise and Meditation

Daily workout or exercise is essential for a healthy body and may have long-term benefits for the depressed people as it temporarily boosts up endorphins (“feel good” chemical and natural anti-depressants), which encourage the mind to think positively and make you happy. You should exercise 3 times a week for a minimum of twenty minutes. You can perform jogging, weight lifting, walking, cycling, rope jumping, and yoga to alleviate depression. Physical activity can be as simple as walking or getting involved in vigorous gym exercises or joining a team sport. Exercise is an easy and cost-effective way to solve the problem of depression, moreover, it does not have any side effects on the body like that of anti-depressant drugs.

  • Do meditation every day for 45 minutes, to overcome depression. Choose a quite place for it. Switch off your phone and regulate your breathing while doing meditation

Have Proper Diet

Ignoring meals, poor diet, craving for sugar are some of the food patterns that lead to depression.  A low-fat diet, comprising of veggies and fruits, is essential for keeping your sugar level stable.  Foods enriched in folic acid and omega-3 fatty acid may reduce mood swings and help ease depression as these foods provide you with instant energy that keeps your body active and fit and helps your mind feel relax.

  • Moreover, serotonin-enhancing diet (popcorn, oatmeal, nuts, egg whites, peanut butter, Cottage cheese, etc) is also considered good for people facing depression. It is the best cure to get over seasonal depression. Eating complex carbohydrate food induces the brain to produce more serotonin. Don’t eat protein-rich diet as it decreases serotonin levels.
  • Vitamin B-12 and folate together produces monoamines like dopamine and serotonin which are responsible to control mood swings and depression. Bupropion, particular dopamine has been medically approved by controlled studies for the treatment of depression. These chemicals directly impact the mood, so you should make your diet vitamin-rich by including cheese, fish, shellfish, bell peppers, spinach, and turkey.
  • The low level of magnesium decreases serotonin level in the brain. Magnesium is a very essential mineral that regulates various biochemical functions in the body and helps deal with depression. It has been proved through various clinical studies that magnesium supplements can effectively treat depression. Take magnesium-rich food such as dark green leafy veggies, nuts, soymilk, boiled spinach, banana, cooked black beans, and roasted cashew.

Set Goals

A depressed person may feel sluggish and sloth, and often complains of lack of concentration. The incomplete tasks may add to your depression level, so it’s better to set daily and realistic goals. The accomplishment of daily small tasks may make you feel good and reduce depression.

Involve in Interesting Activities

Whenever you feel depressed, try to do something of your interest. You can read books, take a culinary or language class, visit a museum or listen to music. These new activities can alter the level of dopamine in your brain, thereby reducing depression.

Lack of sleep may worsen the problem of depression. Therefore, you should get enough sleep to treat yourself.  Set your daily routine and make some changes in your lifestyle. Go to bed at the same time every day to improve your sleeping habits. Sleeping assists you to think better so that you can handle problems without getting stressed.

While sleeping the immune system of our body produces a protein called cytokines. These proteins are needed by our body when we feel depressed or stressed. Lack of sleep can decrease the level of cytokines resulting in symptoms of depression.

Pumpkin Seeds

Pumpkin seeds contain tyrosine, which helps our body to produce mood affecting component called dopamine. People who are depressed have a low level of tyrosine, that is why researchers thought that tyrosine plays an important role in symptoms of depression but studies proved that there is no effect of tyrosine on depression. Although, the L-tryptophan, an amino acid found in pumpkin seeds plays a major role in curing depression

Writing Therapy

Write down your painful and emotional feelings on paper. The writing habit improves your depressed condition and makes you feel lighter. According to a study performed, it is found that expressive writing is an excellent cure for people with Major Depressive Disorder.T his therapy is also found very useful for women who are a sufferer of domestic violence and also for college students.

Sunlight

A Norwegian trial of overweight subjects proved that people given a high dose of vitamin D had less depressive symptoms as compared to others who were given a dose of placebo. This study proved a relation between vitamin D and depression. Get some sunshine to refresh your mood. Vitamin D in sunlight balances the brain hormones, thereby cure depression during fibromyalgia, seasonal affective disorder, and premenstrual syndrome. Use artificial sun lamp during dark weather to reduce seasonal stress.

Apple

Eat an apple with honey and milk, or drink apple juice to rejuvenate your mind. Potassium, vitamin C, vitamin B, and phosphorous in apples prevent nerve cells from damage. Vitamin C enhances the immune system and reduces depression by lowering the level of cortisol, a stress hormone.

 Saffron

Antidepressant drugs have many side effects, therefore herbal psychopharmacology research has increased and the emphasis is on using herbal remedies for the treatment of depression. According to a clinical trial, saffron supplementation can decrease symptoms of depression in adults facing major depressive disorder.   Antidepressant properties of saffron have also been proved in a recent meta-analysis. This analysis depicts the use of saffron to overcome mild-to-moderate depression

Rose Petals

Rose petals have healing properties. Rose oil cures nervous stress and depression. The antidepressant activity of rose petals is based on the fact that it stimulates the β-adrenergic receptors, and inhibits the functioning of the histamine H1 receptors and KCl-related contraction, it also blocks the calcium channels of tracheal chain thereby showing the relaxant activity . Take 20-30 fresh rose petals and boil them in water for fifteen minutes. Add sugar and drink this mixture. Repeat it 2-3 times a day.

Cardamom

Prepare tea and add powdered cardamom seeds to it. Or else, take a cup of hot water and add 2 cardamom’s powder and sugar to it. Sip it slowly.

Coffee

A study proved effective effects of coffee against symptoms of depression. Caffeine, a component of coffee is a central nervous system stimulant, therefore consumption of coffee relieves depression. A study was done in 2011 also proved that drinking coffee decreases the risk of depression among women.

Turmeric

According to a  randomized controlled trial it has been found that Curcumin, a bright yellow compound found in turmeric can be widely used to overcome depression because of its antidepressant properties. Turmeric may prove to be an effective remedy to get rid of depression caused due to seasonal changes. It has been proved in many studies that Curcumin wards off depression by stimulating the process of neurogenesis and increasing the levels of dopamine, norepinephrine, and serotonin.

Ginger Tea

Take 1 tsp of ginger powder and boil it in hot water for a few minutes. Let it cool down. Take it twice a day to cure depression.

Garlic

A study proves that the extract of garlic showed significant antidepressant activity by interacting with the serotonergic, adrenergic and dopaminergic system, and hindering the MAO-A and MAO-B levels. Garlic is one of the best home remedies to overcome chronic depression, insomnia, and fatigue, so add garlic in your daily diet.

Oatmeal

Oatmeal helps overcome anxiety and depression by increasing serotonin levels and decreasing stress hormones, this triggers a feeling of calmness. Take one cup of soy or rice milk and add 4-5 tsp of oatmeal to it. Cook well. Add honey and dry fruits to it. Consume it daily as it relaxes your brain.

Cashew Nuts

Niacin, a form of Vitamin B3 is used in the treatment of depression. Cashew nuts are a good source of Vitamin B3. Take eight cashew nuts and grind them. Have this powder with a glass of milk. Repeat it on regular basis.

Hydrotherapy

Hydrotherapy or water therapy is used in the treatment of various systems like that of the nervous system, Musculoskeletal system, cardiovascular system, etc. Hydrotherapy which is useful for the painful condition is based on the fact that Pressure and temperature of water in this therapy, curbs nociceptors by acting on thermal receptors and mechanoreceptors and exerts a positive effect on spinal segmental mechanisms.

Forty sessions of Ai Chi aquatic exercise (AE) program cures depression in patients facing the problem of multiple sclerosis.

Massage

Massage therapies are based on the fact that mind and body are interconnected. When your body is relaxed, you feel healthy. Touch therapies boost the feeling of calmness in your mind and body, thus helps overcome depression.

The synergistic blend of lavender and bergamot oils provide evidence for its use in medicinal purpose for treating depression. Use this mixture for calming massage. According to the 2007 National Health Interview Survey, it has been concluded that an estimated 18 million U.S. adults and 700,000 children n America used massage therapy for various health-related purposes, including depression.

Acupuncture

Acupuncture is a traditional Chinese therapy which has different styles like that of trigger point acupuncture, single point acupuncture, auricular acupuncture, and traditional/classical acupuncture. The theory of acupuncture is based on the fact of maintaining health by correcting the imbalance of energy in the body. Studies have been performed which resulted that acupuncture is an effective antidepressant monotherapy. But still, further investigations are needed.

Guided Imagery

In this therapy, music, words, and/or visualizations are used to evoke optimistic images in the mind of a depressed person. Positive changes are brought by using the connection between mind and body. An experimental group used A quasi-experimental design to describe the effectiveness of a guided imagery intervention for decreasing depression. The outcome of this study showed significant results in using guided imagery technique to overcome depression.

Light Therapy

If the depression is a seasonal affective disorder (SAD), generally known as ‘winter blues’, caused due to less natural sunlight, then consider light therapy. In this, the depressed person is exposed to a light box for at least ½ an hour every morning. This box imitates the outdoor light which brings chemical changes in the brain, thereby uplift your mood and ease the symptoms of depression. This therapy is about 20 years old. Physicians and clinicians are also trying to find out the efficacy of light therapy for nonseasonal depression.

Cognitive Behavioural Therapy

This is a short-term therapy that focuses on the thoughts of the depressed person and helps develop an optimistic outlook. You can express your thoughts and feelings without any hesitation in front of the therapist. The expert will let you know how to bring positive changes in your behavior and thoughts. It is very useful for moderate depression.

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Dark chocolates

Dark chocolates contain cocoa, which not only satisfies your taste buds, but it also enhances mood and boosts cognitive function by increasing the production of serotonin and endorphin. Many studies have proved that eating dark chocolate daily is very beneficial for people suffering from high anxiety problems.

One study proved the relation between emotional stress and chocolate consumption. They are parallel to each other.

Herbal Remedies for Depression

Below given are some natural remedies for depression.

 Chamomile Tea

A depressed person may experience the problem of insomnia and gastrointestinal disorders that can be cured by flavonoids present in chamomile tea. Prepare tea by adding 2 teaspoons of dried chamomile leaves or a tea bag in a cup of boiling water. Let it steep for 5-7 minutes. Add a little bit of milk and honey if you like. Have a cup of tea daily, thirty minutes before bedtime

Holy Basil Leaves

Holy basil is one of the best remedies to treat depression as it acts as an adaptogen, which helps in the optimal functioning of the body during the depression. Take 1000-2500 mg of leaves per day to reduce the stress level.

Ginseng

Wild Ginseng helps overcome depression caused due to morphine withdrawal by modulating the hypothalamus CRF and NPY systems. Also, Ginseng is an adaptogen, which is a substance that assists the body to survive mental or physical stress. Take one or two grams of ginseng root in the form of powder once a day for 3 months to deal with the depression. You can also take 1 or 2 teaspoons of ginseng tincture 3 times a day to cure the stress.

Lemon Balm Tea

A few comparative studies proved the antidepressant activity of lemon balm. It is also considered as a calming balm and it is traditionally used to alleviate stress, anxiety and depression.  You can use this herb in form of capsules, coated pills or applied topically.  For lemon balm tea, add 1 teaspoon of fresh lemon balm leaves in a cup of boiling water. Steep it for a few minutes. Strain it and drink on a regular basis to treat severe depression.

Asparagus

Methanolic extract of roots of asparagus showed considerable antidepressant activity, that is why this herb is used as an adaptogen. Use dried asparagus roots to make powder. Take one to two grams of this powder once a day to get rid of stress.

Spikenard or Nardostachys

The extracts of Spikenard or Nardostachys acts as a mild sedative and has nerve relaxing properties that induces calming effects on the brain. Use the roots and rhizome of this herb to relieve stress.

Nutmeg

Monoamine hypothesis is the most popular theory for the pathogenesis of depression. According to this theory, the insufficiency of central monoamines like dopamine, 5-hydroxytryptamine, and noradrenaline is responsible for depression. Nutmeg enhances the concentration of these neurotransmitters in the brain, hence it proves to be an outstanding remedy to cure depression. Fragrant Nutmeg, Mitragyna Speciosa is its popular types. The effect of Nutmeg is dose-related.

Take 1/8 tsp of nutmeg powder. Add fresh gooseberry juice to it. Take it thrice a day in order to overcome depression.

Licorice

The antidepressant activity of Licorice extract can be determined by the increase of brain neurotransmitter, dopamine, and norepinephrine. Take licorice powder with milk or drink 1-3 cups of licorice tea to alleviate depression.

Sage and Basil Leaves

Sage is not only useful in treating minor ailments but it also plays a vital role in curing depression. It is available in form of dried leaves, essential oils, liquid extract, and sprays. It is a traditional remedy to boost mood. Mix ¼ tsp of basil leaves and ½ tsp of sage leaves in a cup of hot water to prepare a tea. Take it twice a day to reduce depression.

Lavender

Several human investigations have proved mood stabilizer and neuroprotective properties of lavender. Continuous exposure to lavender oil for 7 days can remarkably remove symptoms of depression.

A study used a quasi-experimental design to find out the effect of aromatherapy on depression using lavender, peppermint, marjoram, eucalyptus and rosemary oils blended in proportions of 2:1:2:1:1. The result showed a significant decrease in depression symptoms. A clinical trial also proved efficient use of lavender oil in postpartum depression. Aroma of this oil, when inhaled for 4 weeks, can help overcome depression after childbirth. The British Pharmacopoeia also approved lavender tincture to fight depression.

  • Take 1 tsp of lavender leaves and boil them with one cup of water. Strain and allow it to cool down. Take the solution thrice a day.
  • Alternatively, you can also add 2 or 4 drops of lavender oil in 3 cups of boiling water. Inhale vapors for curing depression.

Sandalwood Powder

Sandalwood powder soothes the mind and helps get rid of depression. Add some water to the sandalwood powder and apply the resultant paste on the forehead regularly.

Commiphora Mukul

Dry some resins of commiphora mukul. Put them on the burning coal. Inhale the smoke for some time. The herb is good for rejuvenating the mind and strengthening the nervous system.

Bacopa Monnieri 

In a study, it was found that a group of Bacopa Monnieri recipients showed a decrease in depression symptoms.  Also, the standardized methanolic extract of Bacopa monniera was tested for anti depressant properties. The dose of 20 and 40 mg/kg was given for 5 days and it was found that there was considerable antidepressant activity . Take 5 gm of bacopa monnieri and add it to a glass of milk. Consume it once daily. You can also use bacopa monnieri oil to massage your head, in order to deal with depression.

Ginkgo Biloba

Animal studies suggest that Ginkgo biloba extract decreases CRH activity, this activity is significantly associated with mood swings and depression. The dried and crushed leaves of Ginkgo Biloba help relieve stress by stimulating the brain to release neurotransmitters and increasing the blood flow to the brain.

Aromatherapy

The major symptoms of the depression can be treated by aromatherapy. Use essential oils like sandalwood, lavender, basil, ylang-ylang, geranium, angelica, jasmine, chamomile, and rosemary, for spraying in your room or massaging your body. You can also pour a few drops of any of these oils in your bath water for a relaxing experience.

Note – Those people who are allergic to aroma should not use aromatherapy.

Mint 

Many studies proved Peppermint oil’s relaxation-promoting effects on gastrointestinal tissue. The gastrointestinal disorder is one of the stress generated symptom that can be overcome by peppermint oil. Food-based strategies have examined mint for its antidepressant properties.

Note: People suffering from kidney stones, GI a reflux and hiatal hernia should use this remedy cautiously.

Barley Tea

Barley Tea is an outstanding remedy to overcome stress and depression because it helps in the production of tryptophan, an amino acid essential for sleep. This amino acid produces serotonin, a neurotransmitter which controls mood swings.

Passion Flower

According to a recent study it has been found that Passion flower is equivalent to oxazepam, a medically approved anxiolytic drug, used in the treatment of anxiety disorder. You can use this herb to cope with nervous tension, sleep disorder and anxiety

Valerian root

Although there is no scientific evidence on the use of Valerian root, it is safe to use this herb for a short time period of less than a month for the treatment of insomnia and anxiety. This is a traditional remedy to treat depression. Sesquiterpenes fractioned from the root of Valerian is responsible for the antidepressant activity of this herb.

Homeopathic Treatment of Depression

Here are some further details about the top homeopathic remedies for depression.

  • Arsenicum album – It is the best remedy for excessive worriers, especially for those that obsess about health and can be classified as a perfectionist. They often are depressed when they fail to reach personal lofty standards. The person’s symptoms are usually worse in colder weather, and they are also very sensitive to pain.
  • Aurum metallicum – Aurum metallicum is the best remedy for the workaholic with a tendency toward worthlessness, despair, and suicidal thoughts after a failure at work or in their personal life. Symptoms often get worse at night or during the colder months, but these individuals may find relief from calming music.
  • Calcarea carbonica –  Calcarea carbonica is often used for the dependable and industrious types that become overwhelmed from physical illness, work, or worry. The person may also develop fatigue, anxiety, self-pity, discouragement, and confusion. This remedy is also best for people who sweat easily and who suffer from insomnia and periods of sluggishness.
  • Causticum – Causticum is the necessary homeopathic remedy when the person is depressed after a loss or when grieving. Other indications for this remedy include forgetfulness, frequent crying, and mental dullness. The person is often also very sympathetic toward others, and they can have an angry and discouraged world outlook.
  • Cimicifuga – This is the recommended remedy for someone who is energetic and talkative during the good times; however, they feel gloomy and upset during episodes of depression. Other symptoms include neck pain, headaches, and painful menstrual periods.
  • Ignatia amara – Ignatia camera is often best for sensitive people that tend to suppress disappointment or grief. They also do not want to appear too vulnerable, defensive, moody, or guarded in the eyes of others. On occasion, they may burst into tears or laughter for no particular reason. Other symptoms may include abdominal cramps, headaches, or insomnia.
  • Kali phosphoricum – The person that requires kali phosphoricum will likely feel depressed after prolonged periods of emotional stress or excitement. They may also experience nervousness, exhaustion, lack of concentration, headaches, insomnia, anemia, sensitivity to the cold, and indigestion.
  • Lachesis muta – Lachesis muta is the appropriate remedy when depression is caused by suspicion, jealously, or repressed feelings. It is also prescribed for people who dislike commitment or confinement. The person may be worrisome, very talkative, and experience menopausal depression.
  • Natrum carbonicum – Natrum carbonicum is considered the best remedy for people who are selfless, gentle, and mild by nature. The person tends to avoid conflict and usually becomes depressed after a disappointment of some kind. When they feel lonely, they will become isolated, withdrawn, and listen to sad music. Other symptoms will include nervousness and sensitivities to weather changes, sun, and certain foods.
  • Natrum muraticum – The person that requires natrum muraticum will often hide strong inner feelings such as anger, fear of misfortune, grief, or romantic attachment. They are also responsible, reserved, guarded, and they seek solitude. Although they also seek sympathy, they can become angry if someone attempts to console them. Other symptoms include migraines, insomnia, back pain, anxiety, and hopelessness.
  • Phosphoric acid – Phosphoric acid is the best remedy for the person who is dull, indifferent, and apathetic. Other symptoms include loss of appetite and often feeling overwhelmed from overwork, grief, studying, or heartbreak. They also desire juices, often speak in short phrases, and experience night sweats. Depressive episodes often are worse from sleeping.
  • Pulsatilla nigricans – Pulsatilla nigricans is often used for people who become tearful and sad when depressed, and they desire lots of comfort and attention. They are also very moody, jealous, and whiny. The person’s mood will improve with fresh air, crying, and light exercise. Pulsatilla nigricans is the best remedy when depression occurs in conjunction with menopause, menstrual periods, or puberty.
  • Sepia –  Sepia is the best remedy when a person is overwhelmed from loved ones and family members. They will also often want to be alone and they may become angry when bothered. They may feel better after crying and they prefer not to be consoled. Other related symptoms include digestion problems and menstrual issues.
  • Staphysagria – Staphysagria is the best homeopathic remedy for a person who is sensitive, quiet, and emotional. The person may be addicted to work and have a problem standing up to others. The depression can be caused by shame, resentment, suppressed emotions, and hurt feelings. When under too much pressure, they may experience fits of rage. They may also have a high sex drive and experience insomnia, headaches, toothaches, stomachaches, and stress-related bladder infections.

References

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