MOOD DISORDERS

Two groups of mood disorders are broadly recognized; the division is based on whether the person has ever had a manic or hypomanicepisode. 


Thus, there are depressive disorders, of which the best known and most researched is major depressive disorder (MDD)commonly called clinical depression or major depression, and bipolar disorder (BD), formerly known as manic depression and characterized by intermittent episodes of mania or hypomania, usually interlaced with depressive episodes.
Major depression
Depression may be described as feeling sad, blue, unhappy, miserable, or down in the dumps. Most of us feel this way at one time or another for short periods.

True clinical depression is a mood disorder in which feelings of sadness, loss, anger, or frustration interfere with everyday life for weeks or longer.

Bipolar disorder

Bipolar disorder is a condition in which people go back and forth between periods of a very good or irritable mood and depression. The "mood swings" between mania and depression can be very quick.


ATYPICAL ANTIPSYCHOTICS (eg, quetiapine, risperidone):


The effect of atypical antipsychotics as mood stabilizers for the treatment of bipolar disorder can be attributed to a combination of dopamine type 2 (D₂) and serotonin type 2 (5HT₂) antagonism in the CNS.

LITHIUM:


The exact mechanism of lithium as a mood stabilizing agent is unknown. Lithium is a monovalent cation, which competes with other cations (sodium, potassium, calcium, magnesium) at certain receptor sites. In the CNS, lithium is thought to exert its mood stabilizing effect by replacing sodium to inhibit voltage-sensitive sodium channels, causing stabilization of neuronal membranes. In addition, lithium is thought to influence the synthesis, storage, release, and reuptake of norepinephrine, serotonin, and dopamine in the CNS. While effective, lithium monotherapy is rarely used for the treatment of acute mania due to its slow onset of action and need for blood level monitoring.

MONOAMINE OXIDASE INHIBITORS: 


Monoamine oxidase inhibitors (MAOIs) (eg, phenelzine) exert their antidepressant effects by irreversibly and nonselectively blocking the enzymatic activity of both MAO-A and MAO-B. In the CNS, MAO-A primarily metabolizes and inactivates norepinephrine, serotonin, and dopamine whereas MAO-B metabolizes dopamine. Selective inhibitors of MAO-B (eg, selegiline) may be less effective than nonselective agents for the treatment of depression.

Inhibition of neurotransmitter metabolism may persist for up to 2 weeks after discontinuation due to the irreversible nature of MAOIs. Thus, a 2 to 3 week washout period is advisable prior to initiating other antidepressants to avoid drug toxicity or serotonin syndrome. Abrupt cessation of MAOIs should be avoided as withdrawal symptoms may be severe. Due to the complex drug interactions and adverse effects associated with MAOIs, these agents are used less frequently and are reserved for patients who can not tolerate or are unresponsive to other antidepressants.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS: 


Selective serotonin reuptake inhibitors (SSRIs) (eg,sertraline, paroxetine) produce their antidepressant effects by potentiating serotonergic activity through highly specific inhibition of neuronal reuptake of serotonin. SSRIs have a low affinity for adrenergic and muscarinic receptors and have less sedative, anticholinergic, and cardiovascular effects than tricyclic antidepressants. SSRIs with long half lives and active metabolites (eg, fluoxetine) may not be appropriate for those with severe renal or hepatic impairment. When possible, dosage tapering is preferred to abrupt discontinuation to avoid withdrawal symptoms. Concomitant administration of SSRIs with other serotonergic medications can cause serotonin syndrome.

SEROTONIN AND NOREPINEPHRINE REUPTAKE INHIBITORS: 


Serotonin and norepinephrine reuptake inhibitors (SNRIs) (eg, duloxetine, venlafaxine) inhibit the reuptake of both serotonin and norepinephrine to exert their antidepressant effect. Increased noradrenergic activity is believed to reduce the negative symptoms of depression, such as anhedonia, lack of motivation, and psychomotor retardation. Similar to the SSRIs, SNRIs have a low affinity for adrenergic, histaminic, and muscarinic receptors and have similar side effect profiles to SSRIs.

TRICYCLIC ANTIDEPRESSANTS: 


The antidepressant effect of tricyclic antidepressants is not fully understood. Tricyclic antidepressants block neuronal reuptake of norepinephrine and serotonin. In general, secondary amine tricyclics (eg, desipramine, nortriptyline) more selectively inhibit the reuptake of norepinephrine whereas tertiary amine tricyclics (eg, clomipramine, amitriptyline) inhibit both norepinephrine and serotonin. Tertiary amine tricyclics tend to be more sedating and have greater anticholinergic effects than secondary amine tricyclics. Tolerance to these effects may develop with continued use.

OTHER CLASSES:

 Mirtazapine is an antidepressant that potentiates serotonergic and noradrenergic activity in the CNS by acting as an antagonist at presynaptic α₂-adrenergic receptors and serotonin 5-HT₂ and 5-HT₃receptors. Mirtazapine has potent antihistaminic effects that may contribute to its highly sedative effect. The incidence of anticholinergic side effects is low due to moderate antimuscarinic activity.

The antidepressant effect of bupropion can be attributed to its weak inhibition of dopamine and norepinephrine reuptake in the CNS. 


Valproic acid, carbamazepine, and lamotrigine are useful in the treatment of bipolar disorder. Valproic acid is believed to work by increasing concentrations of gamma-aminobutyric acid (GABA). Carbamazepine is thought to exert its actions through prolonged inactivation of voltage-sensitive sodium channels. Similar to lithium, lamotrigine is believed to work by inactivating voltage-sensitive sodium channels, causing stabilization of neuronal membranes.