What are the different neurotransmitters related to psychiatry and the medications associated with them?

Neurotransmitters in Psychiatry and Associated Medications

Core Neurotransmitter Systems

The three primary monoamine neurotransmitters—serotonin, dopamine, and norepinephrine—form the foundation of psychopharmacological treatment in psychiatry, with each system targeting distinct symptom clusters and psychiatric conditions. 1

Serotonin System

Serotonin dysfunction underlies obsessive-compulsive disorder, anxiety disorders, and depression, making selective serotonin reuptake inhibitors (SSRIs) the cornerstone of treatment for these conditions. 1

• SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram) selectively block serotonin reuptake at presynaptic terminals, increasing synaptic serotonin availability 1, 2, 3
• SSRIs demonstrate efficacy in OCD, major depressive disorder, separation anxiety disorder, social phobia, and generalized anxiety disorder in both adults and children 1
• The selective efficacy of serotonin reuptake inhibitors in OCD provided the strongest evidence for serotonin's role in this disorder, though surprisingly little evidence exists for a primary serotonin deficit causing OCD 1
• Serotonin signaling is associated with decreased sensorimotor network activity and increased default-mode network activity, manifesting in distinct behavioral patterns 4

Common pitfall: Serotonin syndrome can occur when SSRIs are combined with other serotonergic agents (triptans, tramadol, fentanyl, lithium, buspirone, St. John's Wort, MAOIs), presenting with agitation, hallucinations, autonomic instability, neuromuscular symptoms, and potentially death 2, 3

Dopamine System

Dopamine dysfunction is central to schizophrenia, psychosis, tic disorders, and reward processing abnormalities, making dopamine receptor antagonists the primary treatment for psychotic disorders. 1

First-Generation (Typical) Antipsychotics

• High-potency agents (haloperidol, fluphenazine, thiothixene) act as strong dopamine D2 receptor antagonists with less sedation but higher risk of extrapyramidal symptoms 1
• Low-potency agents (chlorpromazine, thioridazine) provide more sedation with fewer extrapyramidal symptoms but more anticholinergic and cardiovascular effects 1
• Typical antipsychotics should be avoided when possible in elderly patients due to 50% risk of irreversible tardive dyskinesia after 2 years of continuous use 1

Second-Generation (Atypical) Antipsychotics

• Atypical antipsychotics (risperidone, olanzapine, quetiapine, aripiprazole) act as both serotonin-dopamine receptor antagonists, offering reduced extrapyramidal symptoms and tardive dyskinesia risk compared to typical agents 1, 5
• Risperidone: Start 0.25-2.5 mg/day; extrapyramidal symptoms may occur at doses ≥2 mg/day 1, 6
• Olanzapine: Start 2.5 mg/day at bedtime, maximum 10 mg/day; generally well tolerated 1
• Quetiapine: Start 12.5 mg twice daily, maximum 200 mg twice daily; more sedating with transient orthostasis risk 1, 5
• Aripiprazole represents "third-generation" antipsychotics with partial dopamine receptor agonist activity, distinguishing it from pure antagonists 1

Clinical application: Dopamine signaling increases functional connectivity and activity in the sensorimotor network and salience network while decreasing default-mode network activity 4

Important caveat: Some patients with OCD benefit from augmentation of SSRIs with dopamine D2 receptor antagonists, particularly when OCD overlaps with tic disorders 1

Norepinephrine System

Norepinephrine dysfunction contributes to depression, ADHD, and anxiety, with medications targeting this system addressing specific symptom clusters including attention, energy, and motivation. 7

• SNRIs (venlafaxine, duloxetine, desvenlafaxine) block both serotonin and norepinephrine reuptake, targeting broader depressive symptom profiles 7
• Alpha-2 agonists (clonidine, guanfacine) are recommended for tic disorders and ADHD, preferably administered in the evening due to somnolence/fatigue 6
• Atomoxetine (selective norepinephrine reuptake inhibitor) is particularly useful in tic disorder with comorbid ADHD, as tics do not worsen under treatment 6

Glutamate System

Glutamatergic neurons originating in the prefrontal cortex play an emerging role in OCD pathophysiology, representing a newer target for treatment augmentation. 1

• Glutamatergic dysfunction within cortico-striato-thalamo-cortical (CSTC) circuits contributes to OCD symptoms 1
• Recent studies focus on glutamatergic system modulation as an augmentation strategy when serotonergic and dopaminergic treatments prove insufficient 1

GABA System

GABA, the primary CNS inhibitory neurotransmitter, is targeted by benzodiazepines for acute anxiety and agitation management. 1, 8

• Benzodiazepines (lorazepam, midazolam, diazepam, alprazolam) bind to presynaptic GABA receptors, decreasing neuronal excitability 1, 8
• Lorazepam (2 mg PO/IM) is preferred for acute anxiety attacks due to fast onset, rapid and complete absorption, no active metabolites, and reliable intramuscular absorption 8
• Midazolam offers more rapid onset but shorter duration of action than lorazepam 8
• Diazepam has longer half-life and erratic intramuscular absorption, making it less ideal for acute presentations 8

Critical warning: Benzodiazepines should not be used as monotherapy for long-term anxiety management beyond 2-4 weeks maximum due to tolerance, dependence, and withdrawal risks 8

Geriatric consideration: Avoid benzodiazepines in elderly patients when possible due to increased risk of cognitive impairment, falls, and paradoxical agitation 8

Symptom-Specific Neurotransmitter Targeting

Specific depression symptoms correlate with distinct neurotransmitter deficits, allowing targeted pharmacological intervention. 7

• Decreased positive affect, motivation, pleasure → Dopamine deficit → Dopaminergic agents (bupropion, stimulants) 7
• Increased negative affect, anxiety, rumination → Serotonin/norepinephrine dysfunction → SSRIs, SNRIs 7
• Cognitive symptoms, attention deficits → Norepinephrine/dopamine dysfunction → SNRIs, atomoxetine, stimulants 7

Combination Strategies

When monotherapy fails, combination strategies targeting multiple neurotransmitter systems may be necessary, though evidence is more limited than for single agents. 1

• Combination of benzodiazepine and antipsychotic is frequently recommended for acute agitation in children and adolescents 1, 8
• SSRI augmentation with dopamine D2 receptor antagonists for treatment-resistant OCD 1
• Alpha-2 agonist optimization before adding stimulants in ADHD with comorbid tics, as undertreated ADHD manifests as increased irritability and oppositional behavior 6

Evidence limitation: The evidence base for medication combinations is substantially smaller than for single agents, requiring careful risk-benefit assessment 1