Grief or bereavement

Grief or bereavement (normal and pathological variants): Most individuals recover from grief within a year of bereavement or loss of a loved one. Pathological or complicated grief lasts for > 1 year.

Five stages of grief

Denial
Anger
Bargaining
Depression
Acceptance

It is normal to experience intense sadness and crying, other unfamiliar dysphoric emotions, preoccupation with thoughts and memories of the deceased person, disturbed neurovegetative functions, difficulty concentrating, and relative disinterest in other people and in activities of daily life in acute grief. Auditory or visual hallucinations may occur. It changes to less severe grief, also called integrated grief characterized by sadness, longing for the deceased, allowing the sufferer to move on with their life and participate in social and occupational activities. It is not unusual for bereaved individuals to dream of their deceased loved ones, to look for them in crowds, to sense their presence, feel them watching out for or protecting them, to rehearse discussions or “speak” to them.

Complicated grief is intense grief that lasts longer than 1 year and is characterized by separation distress (recurrent pangs of painful emotions, with intense yearning and longing for the deceased, and preoccupation with thoughts of the loved one) and traumatic distress (sense of disbelief regarding the death, anger and bitterness, distressing, intrusive thoughts related to the death, and pronounced avoidance of reminders of the painful loss). It is associated with impairment in social and occupational functioning. There is increased risk of suicide.

If bereaved individuals meet the criteria for major depression , then they should be treated accordingly.

Antidepressant classes, mechanism of action and adverse effects

Class	Mechanism of action	Adverse effects
Tricyclic antidepressants or TCAs: Amitriptyline, imipramine, clomipramine	Inhibit reuptake transporters for norepinephrine (NE) and serotonin (5HT) in the brain, thus increasing levels in synaptic cleft	Sedation,confusion, postural hypotension, anticholinergic effects, tachycardia, conduction defects, weight gain. “3Cs” - coma, convulsions, cardiotoxicity. Interferes with action of methyldopa, clonidine and guanethidine
Selective serotonin reuptake inhibitors or SSRIs: Fluoxetine, paroxetine, fluvoxamine, citalopram, escitalopram, sertraline	Inhibit SERT or serotonin reuptake transporter thus increasing 5HT levels in the synaptic cleft	Clinical effect may take 3-4 weeks. Nausea, headache, impotence, akathisia, dystonia, seizures
Serotonin norepinephrine reuptake inhibitors or SNRIs: Duloxetine, venlafaxine, desvenlafaxine, levomilnacipran, milnacipran	Inhibit reuptake transporters for 5HT and NE, more selective than TCAs	Withdrawal syndrome is seen after abruptly stopping venlafaxine with anxiety, tremors, palpitations. Duloxetine may cause hepatotoxicity, nausea, increase in BP.
Monoamine oxidase inhibitors or MAOIs: Phenelzine, selegiline, tranylcypromine, isocarboxazid	Inhibit the enzyme MAO thus preventing degradation of NE, 5HT, dopamine and tyramine	Hypertensive crises may occur if consumed with tyramine rich foods like cheese, cured meats, fermented foods, dry fruits. Alcohol, pickled foods, soy sauce etc.
Serotonin 5HT2 antagonists: Trazodone, nefazodone	Block 5HT2A receptor in the CNS	Sedation, severe hepatotoxicity, priapism
Other heterocyclics: Bupropion, amoxapine, mirtazapine	Bupropion: Inhibits reuptake of NE and dopamine. Amoxapine: Inhibits reuptake of NE. Mirtazapine: Blocks inhibitory presynaptic alpha2 receptors and blocks 5HT2 receptors	Bupropion causes anxiety, agitation, psychosis and seizures. Mirtazapine causes weight gain, sedation. Amoxapine causes akathisia, drug induced Parkinsonism, galactorrhea and amenorrhea, cardiotoxicity, seizures.

Antidepressant therapy may be discontinued 6 months after a symptom free period in patients who only had a single episode of depression. Treatment is extended in the presence of recurrence. Patients with major depression contemplating self injury/suicide should be intensively monitored; monitoring may include admission to an inpatient facility, close supervision by family members or by other individuals who know the patient well. Many antidepressants are associated with weight gain , most commonly mirtazapine, phenelzine, paroxetine, amitriptyline, imipramine and doxepin.

Grief or bereavement

Grief or bereavement (normal and pathological variants): Most individuals recover from grief within a year of bereavement or loss of a loved one. Pathological or complicated grief lasts for > 1 year.

Five stages of grief

Denial
Anger
Bargaining
Depression
Acceptance

If bereaved individuals meet the criteria for major depression , then they should be treated accordingly.

Antidepressant classes, mechanism of action and adverse effects

Class	Mechanism of action	Adverse effects
Tricyclic antidepressants or TCAs: Amitriptyline, imipramine, clomipramine	Inhibit reuptake transporters for norepinephrine (NE) and serotonin (5HT) in the brain, thus increasing levels in synaptic cleft	Sedation,confusion, postural hypotension, anticholinergic effects, tachycardia, conduction defects, weight gain. “3Cs” - coma, convulsions, cardiotoxicity. Interferes with action of methyldopa, clonidine and guanethidine
Selective serotonin reuptake inhibitors or SSRIs: Fluoxetine, paroxetine, fluvoxamine, citalopram, escitalopram, sertraline	Inhibit SERT or serotonin reuptake transporter thus increasing 5HT levels in the synaptic cleft	Clinical effect may take 3-4 weeks. Nausea, headache, impotence, akathisia, dystonia, seizures
Serotonin norepinephrine reuptake inhibitors or SNRIs: Duloxetine, venlafaxine, desvenlafaxine, levomilnacipran, milnacipran	Inhibit reuptake transporters for 5HT and NE, more selective than TCAs	Withdrawal syndrome is seen after abruptly stopping venlafaxine with anxiety, tremors, palpitations. Duloxetine may cause hepatotoxicity, nausea, increase in BP.
Monoamine oxidase inhibitors or MAOIs: Phenelzine, selegiline, tranylcypromine, isocarboxazid	Inhibit the enzyme MAO thus preventing degradation of NE, 5HT, dopamine and tyramine	Hypertensive crises may occur if consumed with tyramine rich foods like cheese, cured meats, fermented foods, dry fruits. Alcohol, pickled foods, soy sauce etc.
Serotonin 5HT2 antagonists: Trazodone, nefazodone	Block 5HT2A receptor in the CNS	Sedation, severe hepatotoxicity, priapism
Other heterocyclics: Bupropion, amoxapine, mirtazapine	Bupropion: Inhibits reuptake of NE and dopamine. Amoxapine: Inhibits reuptake of NE. Mirtazapine: Blocks inhibitory presynaptic alpha2 receptors and blocks 5HT2 receptors	Bupropion causes anxiety, agitation, psychosis and seizures. Mirtazapine causes weight gain, sedation. Amoxapine causes akathisia, drug induced Parkinsonism, galactorrhea and amenorrhea, cardiotoxicity, seizures.