5.2 Antidepressants and mood stabilizers

Antidepressants and mood stabilizers are key players in treating mental health disorders. These drugs work by tweaking brain chemistry, helping to balance mood and emotions. From SSRIs to lithium, each medication has its own unique way of improving mental well-being.

Understanding how these drugs work is crucial for effective treatment. We'll look at their mechanisms, effects, and uses. We'll also explore potential side effects and interactions, giving you a well-rounded view of these important medications.

Antidepressant Mechanisms of Action

Classification of Antidepressants

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• Antidepressants categorized into several classes based on primary mechanism of action in the brain (MAOIs, TCAs, SSRIs, SNRIs, and atypical antidepressants)
• MAOIs inhibit enzyme monoamine oxidase responsible for breaking down neurotransmitters (serotonin, norepinephrine, and dopamine)
• TCAs block reuptake of serotonin and norepinephrine with varying degrees of selectivity
• SSRIs selectively inhibit serotonin reuptake in synaptic cleft increasing its availability
• SNRIs inhibit reuptake of both serotonin and norepinephrine affecting multiple neurotransmitter systems simultaneously
• Atypical antidepressants have diverse mechanisms
  • Antagonism of specific receptors
  • Modulation of neurotransmitter release
  • Enhancement of neuroplasticity

Detailed Mechanisms of Action

• MAOIs prevent breakdown of monoamine neurotransmitters
  • Increase overall levels of serotonin, norepinephrine, and dopamine in the brain
  • Examples include phenelzine and tranylcypromine
• TCAs block reuptake transporters for serotonin and norepinephrine
  • Also affect other neurotransmitter systems (histamine and acetylcholine)
  • Examples include amitriptyline and nortriptyline
• SSRIs selectively target serotonin transporter (SERT)
  • Increase serotonin levels in synaptic cleft
  • Examples include fluoxetine and sertraline
• SNRIs inhibit both serotonin and norepinephrine transporters
  • Increase levels of both neurotransmitters
  • Examples include venlafaxine and duloxetine
• Atypical antidepressants have unique mechanisms
  • Bupropion inhibits dopamine and norepinephrine reuptake
  • Mirtazapine antagonizes adrenergic and serotonergic receptors
  • Vortioxetine modulates multiple serotonin receptors and inhibits serotonin reuptake

Pharmacological Effects of SSRIs, SNRIs, and TCAs

SSRI Effects and Characteristics

• SSRIs selectively block serotonin transporter (SERT) increasing serotonin levels in synaptic cleft
• Enhance serotonergic neurotransmission leading to mood elevation and reduced anxiety
• Improve sleep patterns and regulate appetite
• Delayed onset of action typically 2-4 weeks for full therapeutic effect
• Generally well-tolerated with fewer side effects compared to older antidepressants
• Examples of SSRIs include fluoxetine, sertraline, and escitalopram

SNRI Mechanisms and Impacts

• SNRIs inhibit reuptake of both serotonin and norepinephrine
• Increase levels of these neurotransmitters in synaptic cleft
• Dual action leads to improvements in mood, energy levels, and pain perception
• Effective for both depression and certain anxiety disorders
• May have faster onset of action compared to SSRIs in some patients
• Useful in treating chronic pain conditions (fibromyalgia, neuropathic pain)
• Examples of SNRIs include venlafaxine, duloxetine, and desvenlafaxine

TCA Pharmacology and Effects

• TCAs block reuptake of serotonin and norepinephrine
• Affect other neurotransmitter systems (histamine and acetylcholine)
• Broad pharmacological profile contributes to efficacy in treating depression
• Lead to wider range of side effects compared to SSRIs and SNRIs
• Lower therapeutic index requiring careful dosing and monitoring
• Potent in treating severe depression and certain pain conditions
• Examples of TCAs include amitriptyline, nortriptyline, and imipramine

Mood Stabilizers for Bipolar Disorder

Lithium as a Mood Stabilizer

• Lithium modulates multiple neurotransmitter systems and intracellular signaling pathways
• Leads to neuroprotective and mood-stabilizing effects
• Prevents or reduces severity of manic, hypomanic, and depressive episodes
• Requires regular monitoring of serum levels due to narrow therapeutic index
• Potential for toxicity manifesting as tremors, cognitive impairment, and renal dysfunction
• Effective in reducing suicide risk in bipolar patients
• Used as first-line treatment for bipolar disorder, especially for classic presentations

Anticonvulsants as Mood Stabilizers

• Anticonvulsants (valproic acid, carbamazepine, lamotrigine) used as mood stabilizers
• Modulate neuronal excitability and neurotransmitter release
• Help maintain emotional equilibrium by preventing extreme mood swings
• Valproic acid effective for manic episodes and mixed states
• Carbamazepine useful for rapid-cycling bipolar disorder
• Lamotrigine particularly effective for bipolar depression
• Side effects may include weight gain, sedation, and hepatotoxicity

Therapeutic Considerations for Mood Stabilizers

• Mood stabilizers often used in combination with antipsychotics or antidepressants
• Provide comprehensive treatment for bipolar disorder
• Therapeutic effects typically develop over several weeks
• Necessitate long-term, consistent use for optimal management
• Regular monitoring required for efficacy and side effects
• Dosage adjustments may be needed based on clinical response and tolerability
• Patient education crucial for adherence and safety

Therapeutic Uses of Antidepressants and Mood Stabilizers

Applications of Antidepressants

• Primarily used to treat major depressive disorder
• Therapeutic applications in anxiety disorders (generalized anxiety disorder, panic disorder)
• Effective for obsessive-compulsive disorder (OCD)
• Used in certain pain conditions (neuropathic pain, fibromyalgia)
• SSRIs and SNRIs first-line treatments for many psychiatric disorders
• TCAs used for treatment-resistant depression and certain pain syndromes
• Atypical antidepressants offer alternatives for patients unresponsive to or intolerant of other options

Mood Stabilizer Indications

• Primarily indicated for bipolar disorder (manic, hypomanic, and depressive episodes)
• Used in treatment-resistant depression as augmentation strategy
• Applied in certain anxiety disorders (off-label use)
• Lithium effective in reducing suicidal behavior in bipolar patients
• Valproic acid and carbamazepine useful for rapid-cycling bipolar disorder
• Lamotrigine particularly effective for bipolar depression
• Mood stabilizers sometimes used in schizoaffective disorder

Adverse Effects and Drug Interactions

• SSRIs and SNRIs common adverse effects include nausea, sexual dysfunction, and sleep disturbances
• TCAs may cause anticholinergic effects (dry mouth, constipation, blurred vision)
• Mood stabilizers require careful monitoring due to potential for serious side effects
• Lithium toxicity can lead to tremors, cognitive impairment, and renal dysfunction
• Anticonvulsant mood stabilizers may cause weight gain, sedation, and hepatotoxicity
• Significant drug interactions occur between antidepressants and medications metabolized by cytochrome P450 enzymes
• MAOIs combined with other antidepressants or tyramine-rich foods can cause hypertensive crises