Antidepressants, Antipsychotics, and Nursing

• Antidepressants, antipsychotics, and anticonvulsants are major medication classes for psychiatric and neurological conditions.
• Nursing is crucial for medication management, including administration, monitoring, and education.

Antidepressants

• Primarily target neurotransmitter systems to alleviate symptoms of depression, anxiety, and mood disorders
• These drugs modulate neurotransmitter activity, receptor interactions, and long-term neural adaptations.
• Key neurotransmitters: serotonin, norepinephrine, and dopamine

Neurotransmitter Modulation

• Antidepressants mainly affect serotonin, norepinephrine, and dopamine neurotransmitter systems.
• Selective Serotonin Reuptake Inhibitors (SSRIs) block serotonin reuptake.
• SSRI examples: fluoxetine, sertraline, paroxetine, citalopram, and escitalopram
• SSRIs are commonly prescribed due to favorable side effect profiles.
• SSRIs block the reuptake of serotonin, increasing its availability in the synaptic cleft.
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) inhibit serotonin and norepinephrine reuptake.
• SNRI examples: venlafaxine, duloxetine, and desvenlafaxine
• SNRIs are effective for depression, anxiety, and certain pain conditions.
• SNRIs inhibit the reuptake of both serotonin and norepinephrine, enhancing their synaptic concentrations.
• Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs) primarily inhibit the reuptake of norepinephrine and dopamine.
• Tricyclic Antidepressants (TCAs) block serotonin and norepinephrine reuptake and affect other receptors
• TCA examples: amitriptyline, nortriptyline, and imipramine
• TCAs are less common as first-line agents due to side effects and overdose potential.
• TCAs inhibit the reuptake of serotonin and norepinephrine, but also affect other receptors, leading to more side effects.
• Monoamine Oxidase Inhibitors (MAOIs) inhibit monoamine oxidase, which breaks down serotonin, norepinephrine, and dopamine.
• MAOI examples: phenelzine, tranylcypromine, and selegiline
• MAOIs require strict dietary restrictions to avoid hypertensive crises with tyramine.
• MAOIs inhibit the enzyme monoamine oxidase, which breaks down serotonin, norepinephrine, and dopamine, increasing their levels.
• Serotonin Modulators affect serotonin receptors and transporters in various ways, such as antagonism or partial agonism.
• Other antidepressants: bupropion (dopamine-norepinephrine reuptake inhibitor), mirtazapine (alpha-2 adrenergic antagonist), and trazodone (serotonin modulator).

Receptor Interactions

• Antidepressants interact with various receptors, influencing their therapeutic and side effect profiles.
• SSRIs primarily target the serotonin transporter (SERT).
• SNRIs target both SERT and the norepinephrine transporter (NET).
• TCAs affect serotonin and norepinephrine transporters and also bind to histamine, acetylcholine, and adrenergic receptors.
• MAOIs inhibit monoamine oxidase A and B, reducing the breakdown of monoamine neurotransmitters.
• Serotonin modulators like trazodone and nefazodone act as serotonin receptor antagonists and reuptake inhibitors.
• Mirtazapine is an alpha-2 adrenergic antagonist, enhancing norepinephrine and serotonin release, and also blocks histamine (H1) receptors.

Long-term Neural Adaptation

• Chronic antidepressant use leads to long-term changes in neural function and structure.
• These adaptations include alterations in receptor sensitivity, gene expression, and neurogenesis.
• Receptor Desensitization: Prolonged exposure to increased neurotransmitter levels can cause postsynaptic receptors to become less responsive.
• Upregulation/Downregulation of Receptors: Antidepressants can cause the number of receptors to increase (upregulation) or decrease (downregulation) over time.
• Neurotrophic Effects: Some antidepressants promote neurogenesis and increase levels of brain-derived neurotrophic factor (BDNF), supporting neuronal survival and growth.
• Synaptic Plasticity: Antidepressants can enhance synaptic connections and plasticity, improving overall brain function.

Pharmacological Classifications

• Antidepressants are categorized into several classes based on their mechanisms of action.
• Selective Serotonin Reuptake Inhibitors (SSRIs): Include drugs like fluoxetine, sertraline, paroxetine, citalopram, and escitalopram.
• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Include venlafaxine, duloxetine, and desvenlafaxine.
• Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs): Primarily bupropion.
• Tricyclic Antidepressants (TCAs): Include amitriptyline, nortriptyline, imipramine, and desipramine.
• Monoamine Oxidase Inhibitors (MAOIs): Include phenelzine, tranylcypromine, and isocarboxazid.
• Serotonin Modulators: Include trazodone, nefazodone, and vortioxetine.
• Tetracyclic Antidepressants: Include mirtazapine.
• Common antidepressant side effects: nausea, headache, insomnia, sexual dysfunction, and weight changes.
• Serotonin syndrome is life-threatening, caused by excessive serotonin activity.
• Serotonin syndrome symptoms: agitation, confusion, tachycardia, hypertension, muscle rigidity, and hyperthermia.
• Discontinuation syndrome occurs with abrupt cessation, causing dizziness, nausea, anxiety, and flu-like symptoms.
• Antidepressants can increase suicidal thoughts/behaviors, especially in young individuals.
• Monitor patients closely for mood or behavior changes, especially during initial treatment and dosage adjustments.

Side Effects and Contraindications

• Antidepressants can cause various side effects, which differ among the drug classes.
• SSRIs: Common side effects include nausea, insomnia, sexual dysfunction, and weight gain.
• SNRIs: Similar side effects to SSRIs, plus increased blood pressure and heart rate in some individuals.
• NDRIs: Can cause anxiety, insomnia, and a lower risk of sexual side effects.
• TCAs: Side effects include dry mouth, constipation, blurred vision, urinary retention, orthostatic hypotension, and cardiac arrhythmias.
• MAOIs: Can cause orthostatic hypotension, weight gain, insomnia, and interactions with tyramine-rich foods leading to hypertensive crisis.
• Serotonin Modulators: Trazodone can cause sedation and priapism; nefazodone has a risk of liver toxicity; mirtazapine can cause sedation and weight gain.
• Contraindications: Specific to each drug, but generally include hypersensitivity to the drug, concurrent use of MAOIs, and certain cardiac conditions.
• SSRIs and SNRIs are generally better tolerated than TCAs and MAOIs.
• MAOIs require strict dietary restrictions to avoid tyramine-induced hypertensive crises.
• Antidepressants may increase the risk of suicidal thoughts, especially in young adults.
• Drug interactions are common, especially with TCAs and MAOIs.
• Serotonin syndrome is a potentially life-threatening condition that can occur when combining serotonergic drugs.
• Discontinuation syndrome can occur when antidepressants are abruptly stopped, particularly with SSRIs and SNRIs; symptoms include flu-like symptoms, insomnia, nausea, and anxiety.

Antipsychotics

• Primarily used for psychotic disorders like schizophrenia, bipolar disorder, and psychotic depression.
• Affect dopamine and other neurotransmitter systems.
• First-Generation Antipsychotics (FGAs) block dopamine D2 receptors.
• FGAs are also known as typical antipsychotics or neuroleptics.
• FGA examples: haloperidol, chlorpromazine, and fluphenazine
• FGAs reduce positive symptoms of psychosis but have a higher risk of extrapyramidal symptoms (EPS).
• Second-Generation Antipsychotics (SGAs) affect dopamine and serotonin receptors.
• SGAs are also known as atypical antipsychotics.
• SGA examples: risperidone, olanzapine, quetiapine, aripiprazole, and ziprasidone
• SGAs are generally preferred due to a lower EPS risk but have a higher risk of metabolic side effects.
• Extrapyramidal Symptoms (EPS) include acute dystonia, parkinsonism, akathisia, and tardive dyskinesia (TD).
• Tardive dyskinesia is a potentially irreversible movement disorder.
• Neuroleptic Malignant Syndrome (NMS) is a rare, life-threatening reaction to antipsychotics
• NMS symptoms: fever, muscle rigidity, altered mental status, and autonomic dysfunction
• Metabolic side effects of SGAs: weight gain, hyperglycemia, dyslipidemia, and increased risk of type 2 diabetes.
• Antipsychotics can prolong the QT interval, increasing the risk of torsades de pointes.
• Monitor patients on antipsychotics for metabolic changes, EPS, NMS, and cardiac effects.

Anticonvulsants

• Primarily used to treat seizures, but also effective in managing mood disorders like bipolar disorder.
• Work by stabilizing neuronal activity in the brain.
• Mood-stabilizing anticonvulsants: valproate, lamotrigine, carbamazepine, and oxcarbazepine.
• Valproate treats mania and mixed episodes in bipolar disorder.
• Valproate side effects: weight gain, hair loss, tremor, and liver toxicity.
• Valproate is contraindicated in pregnancy due to the risk of birth defects.
• Lamotrigine treats bipolar depression and prevents mood episodes.
• Lamotrigine has a risk of Stevens-Johnson syndrome (SJS).
• Carbamazepine treats mania and mixed episodes in bipolar disorder.
• Carbamazepine can cause blood dyscrasias, liver toxicity, and SJS.
• Oxcarbazepine is similar to carbamazepine but with a lower risk of side effects.
• Common anticonvulsant side effects: drowsiness, dizziness, nausea, and headache.
• Some anticonvulsants can interact with other medications, including hormonal contraceptives.
• Monitor patients on anticonvulsants for mood changes, side effects, and therapeutic drug levels.
• Anticonvulsants prevent or control seizures through various mechanisms.

Mechanisms of Action for Anticonvulsants

• These mechanisms include modulation of ion channels, neurotransmitter inhibition, receptor interaction, metabolic pathways, and neuroprotective effects

Ion Channel Modulation

• Voltage-gated sodium channels are crucial for the generation and propagation of action potentials in neurons
• Many anticonvulsants, like phenytoin, carbamazepine, and lamotrigine, prolong the inactivation state of sodium channels
• This reduces the ability of neurons to fire at high frequencies, thus preventing the spread of seizure activity
• Calcium channels play a role in neurotransmitter release and neuronal excitability
• Some anticonvulsants, such as gabapentin and pregabalin, bind to the α2δ subunit of voltage-gated calcium channels
• This reduces calcium influx and neurotransmitter release
• T-type calcium channels are involved in thalamocortical oscillations, which are important in certain types of seizures
• Ethosuximide is a specific T-type calcium channel blocker, used primarily for absence seizures
• Potassium channels help regulate neuronal excitability by hyperpolarizing the cell membrane
• Retigabine (ezogabine) enhances the function of KCNQ2-5 potassium channels
• This stabilizes the resting membrane potential and reduces neuronal excitability

Neurotransmitter Inhibition

• Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain
• Anticonvulsants can enhance GABAergic neurotransmission through several mechanisms
• Some drugs, like benzodiazepines and barbiturates, bind to the GABAA receptor and enhance its response to GABA
• Tiagabine inhibits GABA reuptake, increasing the concentration of GABA in the synaptic cleft
• Vigabatrin irreversibly inhibits GABA transaminase (GABA-T), the enzyme responsible for GABA degradation which increases GABA levels in the brain
• Glutamate is the primary excitatory neurotransmitter in the brain.
• Excessive glutamatergic activity can contribute to seizures
• Some anticonvulsants reduce glutamate release or block glutamate receptors
• Lamotrigine and topiramate can reduce glutamate release
• Perampanel is a selective non-competitive antagonist of the AMPA glutamate receptor

Receptor Interaction

• Anticonvulsants can interact with various receptors to modulate neuronal excitability
• The GABAA receptor is a major target for anticonvulsant drugs
• Benzodiazepines, barbiturates, and some newer drugs bind to different sites on the GABAA receptor
• This enhances GABA-mediated inhibition
• Glutamate receptors, including AMPA, NMDA, and kainate receptors, are involved in excitatory neurotransmission
• Perampanel blocks the AMPA receptor
• Felbamate blocks the NMDA receptor and enhances GABAergic transmission
• Some anticonvulsants interact with other receptors, such as adenosine receptors and cannabinoid receptors, to exert their effects
• These interactions may contribute to the anticonvulsant and neuroprotective properties of these drugs

Metabolic Pathways

• Some anticonvulsants affect metabolic pathways in the brain to reduce seizure activity
• Topiramate inhibits carbonic anhydrase, an enzyme involved in the production of bicarbonate ions
• This can reduce neuronal excitability
• Valproic acid affects fatty acid metabolism and mitochondrial function
• This can influence neuronal excitability and protect against neuronal damage

Neuroprotective Effects

• Besides their anticonvulsant properties, some drugs have neuroprotective effects
• These effects can help prevent neuronal damage and cell death associated with seizures
• Mechanisms involved in neuroprotection include reducing oxidative stress, inhibiting apoptosis, modulating inflammation, and enhancing neurotrophic factors
• Drugs with neuroprotective properties include valproic acid, topiramate, and lamotrigine
• Neuroprotection is important for long-term seizure management and aims to prevent progressive brain damage associated with recurrent seizures

Nursing Role

• Medication Administration: Ensuring the right patient gets the right medication, dose, route, and time.
• Monitoring Therapeutic Effects: Assessing patient response and documenting symptom improvement.
• Monitoring Adverse Effects: Regularly assess for side effects and report concerns promptly.
• Patient Education: Providing information about the medication's purpose, dosing, side effects, and interactions.
• Monitoring Adherence: Assessing adherence and providing support to improve it.
• Coordinating Care: Collaborating with healthcare professionals for comprehensive care.
• Providing Emotional Support: Offering support, addressing concerns, and promoting coping strategies.
• Documenting and Reporting: Accurately documenting and reporting medication administration, patient responses, and adverse effects.
• Medication Reconciliation: Reviewing medication lists to identify potential interactions or duplications.
• Special Populations: Considering unique needs of pregnant women, children, and elderly patients.
• Knowledge of drug interactions is required between antidepressants, antipsychotics, and anticonvulsants, as well as interactions with other medications
• Nurses must know the signs/symptoms of serotonin syndrome, NMS, and SJS and be prepared to intervene.
• Nurses educate patients about medication adherence and strategies to manage side effects.
• Nurses should assess patients for suicidal ideation and take appropriate precautions.
• Nurses should advocate for patients' rights and ensure they receive the best possible care.
• Nurses should stay up-to-date on the latest research and guidelines.