6. Neurological Drugs and Psychotropics

DENT 4217: Neurological drugs and psychotropics¹

Overview

This lecture provides an overview of key neurological and psychotropic medications, focusing on their mechanisms, adverse effects, and specific implications for dental practice. The content serves as a consolidation of knowledge from DENT3005, with an emphasis on practical application through case scenarios.

Learning Outcomes²

1. Consolidate and build upon foundational pharmacological knowledge from DENT3005
2. Identify commonly prescribed psychiatric and neurological medications
3. Understand and evaluate potential drug interactions in the dental setting
4. Identify oral and dental side effects associated with psychiatric and neurological pharmacotherapies
5. Apply this knowledge to tailor dental treatment plans based on a patient’s medical history and pharmacological profile
6. Demonstrate clinical reasoning in case-based scenarios involving patients on neurological and psychiatric medications

Neurological drugs³

Note

The human nervous system is a complex network governing all bodily functions. Neurological disorders can significantly disrupt this system, often requiring lifelong management. This lecture focuses on the pharmacotherapy for several major neurological conditions frequently encountered in clinical practice.

• Epilepsy
• Parkinson’s disease
• Migraine
• Alzheimer’s disease
• Multiple sclerosis

Note

While the lecturer intended to cover Epilepsy, Parkinson’s Disease, Alzheimer’s Disease, Migraine, and Multiple Sclerosis, the latter two were omitted due to time constraints.

Epilepsy⁴

• Seizures: transient uncontrolled electrical discharges
  • Causes: biochemical imbalance, structural
  • Partial Vs generalized
• Epilepsy: recurrent, unprovoked seizure, different types

Clarification

It is important to distinguish this from a provoked seizure, which can occur due to temporary conditions like high fever or drug withdrawal and is not considered epilepsy.

• Pharmacological targets
  • Inhibitory GABA Vs excitatory glutamatergic pathways
  • Voltage gated membrane channels

Seizure Characteristics⁵

Note

A seizure is a symptom resulting from a transient, abnormal, and uncontrolled electrical discharge in the brain’s cerebral cortex.

• Focal Seizure: The discharge is localized to a specific brain region.
• Generalised Seizure: The discharge involves a larger area of the brain.
• Note: The term

Seizure	Characteristics
Absence (generalized)	Sudden transient loss of consciousness
Myoclonic (generalized)	Convulsive movements of body
Tonic (generalized)	Muscle contractions forcing body into rigid & fixed positions
Tonic-clonic (generalized)	Collapse, followed by rigidity then violent convulsions, and deep seep postictally, unresponsiveness, deep confusion
Aura (simple partial)	Usually experiencing sedation (e.g. olfactory, visual or aural) w/ no stimulus present
Jacksonian (simple partial)	Muscle spasms characterized by sequential involvement of body parts
Psychomotor (complex partial)	Transient aberrant behavior such as mood alteration, psychotic behavior or apparent drunkenness

Antiepileptics⁶

Treatment Goal and Initiation

The primary goal of antiepileptic drug (AED) therapy is the prevention of seizures and their associated complications, such as physical injury and reduced quality of life. AEDs are also used for the acute treatment of severe conditions like status epilepticus.

Treatment Initiation:

• Treatment typically begins when the risk of further seizures outweighs the potential risks of drug therapy.
• After a first seizure, recurrence occurs in 30-50% of individuals, so medication is not always started immediately.
• Treatment is clearly indicated after two or more unprovoked seizures within a 6-12 month period.

	First line	Second line
Focal (partial) seizures	carbamazepine¹,	clobazam, lamotrigine¹, levetiracetam¹, oxcarbazepine, phenobarbital, phenytoin, pregabalin, tiagabine, topiramate, valproate, zonisamide
Generalised tonic-clonic seizures	valproate,	carbamazepine², clobazam, lamotrigine¹, oxcarbazepine², phenobarbital, phenytoin², topiramate
Absence seizures	ethosuximide³, valproate,	clonazepam, lamotrigine
Myoclonic seizures	valproate,	clonazepam, levetiracetam, phenobarbital
Infantile spasms	prednisolone, tetracosactide,	vigabatrin⁴, clonazepam, valproate

¹ may be first line in females of child-bearing potential
² do not use if juvenile myoclonic epilepsy is suspected (often presents with a tonic-clonic seizure) as it may be ineffective or worsen seizures
³ does not prevent generalised tonic-clonic seizures which often coexist in juvenile absence epilepsy
⁴ use only if no safer alternative

Antiepileptic Drug Classes⁷

Barbiturates

• MOA: Prolong inhibitory postsynaptic potential

It depresses neuronal excitability by enhancing chloride ion influx at the GABA-A receptor, leading to membrane hyperpolarization.

• Drug interactions
  • Phenobarbital + metronidazole

Phenobarbital increases the metabolism of metronidazole, potentially reducing its effectiveness. The dose of metronidazole may need to be increased.

• Other CNS depressants: monitor sedation

• CYP3A4 substrates: clarithromycin, codeine, erythromycin, azoles, oxycodone, tramadol…

• ADR

  • Sedation, cognitive impairment, altered mood and behaviour
  • [Rare]: exfoliative dermatitis

• Induction of liver enzymes (e.g., CYP3A4), affecting the metabolism of many other drugs.

• Risk of physical dependence with long-term use.

Generic name	Brand Name
Phenobarbital	Phenobarb
Primidone	Mysoline

Benzodiazepines⁸

• MOA: potentiate inhibitory effect of GABA
• Drug interactions
  • Other CNS depressants: monitor sedation
  • Alprazolam: itraconazole, ketoconazole → enhance sedation & respiratory depression
  • Diazepam + fluconazole → increase adverse effect
  • Midazolam + [CYP3A4 inh] → enhance sedation & respiratory depression
• ADR: fatigue, drowsiness, muscle weakness, ataxia, dry mouth, hypersalivation 😊 and many more

Note on Hypersalivation

Hypersalivation can occur paradoxically if sedation and muscle relaxation impair the swallowing reflex, leading to saliva pooling and drooling.

Generic name	Brand Name
Clobazam	Frisium
Clonazepam	Rivotril
Diazepam	Valium
Lorazepam	Lorazepam inj
Midazolam	Hypnovel inj

Ataxia refers to a loss of coordination and balance, resulting in clumsy or awkward movements, often affecting walking, speech, and fine motor skills.

Gabapentinoids⁹

• MOA: bind to alpha-2 delta protein subunit of high threshold voltage-dependent calcium channels → reduce calcium influx & neurotransmitter release

They are structurally similar to GABA but do not act on GABA receptors.

• Drug interactions: other CNS depressants
• ADR
  • Drowsiness, sedation, dizziness, vertigo
  • Dysarthria
  • Ataxia
  • Tremor
  • Dry mouth
  • [Rare]: Steven Johnson’s syndrome

Generic name	Brand Name
Gabapentin	Neurontin
Pregabalin	Lyrica

Summary of Selected Antiepileptics and ADRs¹⁰

Note

Most antiepileptics can cause some degree of drowsiness or dizziness, especially at the start of treatment or during dose adjustments. Dentists should be aware of several key neurological side effects:

• Ataxia: Loss of coordination and balance.
• Orofacial Dyskinesia: Involuntary movements of the face and mouth.
• Hypokinesia: Excessive or abnormal muscle activity, making patients restless.
• Aphasia: Difficulty with speaking or understanding language.
• Nystagmus: Rapid, involuntary eye movements.
• Serious Skin Reactions: Be vigilant for early signs of SJS or Toxic Epidermal Necrolysis (TEN), which can manifest on the face and oral mucosa.

Selected drug (brand)	Selected ADR
Carbamazepine (Tegretol)	[common]: drowsiness, ataxia, dizziness, dry mouth [rare]: severe skin reactions, orofacial dyskinesia
Ethosuximide (Zarontin)	[common]: dizziness, drowsiness, ataxia [rare]: Steven Johnson’s
Lamotrigine (Lamictal)	[common]: dizziness, ataxia, hyperkinesia [rare]: severe skin reactions
Levetiracetam (Keppra)	[common]: drowsiness, dizziness, vertigo, ataxia [rare]: severe skin reactions
Oxcarbazepine (Trileptal)	[common]: dizziness, tremor, ataxia, nystagmus [rare]: severe skin reactions
Phenytoin (Dilantin)	[common]: sedation, ataxia, nystagmus, vertigo, gingival hyperplasia [rare]: severe skin reactions
Topiramate (Topamax)	[common]: dizziness, nervousness, agitation, speech disorder [infrequent]: aphasia, nystagmus, taste disturbance
Valproate (Epilim)	[common]: ataxia, dizziness, tremor

Epilepsy: Dental Implications¹¹

Pharmacological Considerations

• Drug interactions

  • CNS depressants
  • CYP3A4

• ADR

  • [common]: drowsiness, oversedation, cognitive impairment, altered mood and behaviour, lightheadedness, hypersalivation, ataxia, dizziness, vertigo, dysarthria, tremor, dry mouth, nystagmus, taste disturbances
  • [rare]: serious skin reactions
  • Phenytoin: gingival hyperplasia

• Drowsiness/Dizziness: Assist patients when moving in the dental chair.

• Hypersalivation: Can interfere with resin-based restorations; use of a rubber dam is recommended.

• Dry Mouth (Xerostomia): Increases caries risk.

• Motor Disturbances (e.g., tremor): Can make procedures like taking radiographs difficult.

• Gingival Hyperplasia: A known side effect of phenytoin, complicating oral hygiene and increasing periodontal disease risk. Meticulous care is essential, and referral to the GP for medication review may be necessary.

Patient Management¹²

• Patient management

• Appointment when the concentration of the antiepileptic medication is the most optimal

• Avoid potential triggers

• Ask patients if they experience a pre-seizure warning sign (aura).

• Know first aid protocols

  • DRSABCD
  • Clear AW
  • Supine position
  • Remove dangerous equipment
  • Protect patient: injury & falls
  • No attempt should be made to open the patient’s mouth
  • Call medical services

In-Chair Seizure Management

1. Immediately remove all sharp instruments.
2. Place the patient in a supine position.
3. Follow the DR’S ABCD emergency protocol.
4. Ensure the airway is clear, but never force anything into the patient’s mouth to avoid fractures, lacerations, or injury to the dental professional.
5. Call for emergency services.

Case Studies: Epilepsy¹³

Case 1: Mr Shake Scaler

Scenario: Mr SS, 29-year-old male with known epilepsy suddenly experiences a generalized tonic-clonic seizure mid-treatment. The dental chair is reclined, and several sharp instruments on the dental tray, operator side

Management:

• Immediate Steps: Remove dangerous instruments, keep the patient supine, follow emergency protocols, clear the airway without force, and call for emergency services.
• Potential Complications: Fractured teeth, soft tissue lacerations, injury to the dental team.
• Prevention: Avoid triggers, schedule appointments when medication is at optimal levels, and maintain regular communication with the patient’s GP. Emphasize meticulous plaque control and schedule regular cleanings (e.g., 3-6 monthly).

Case 2: Ms Seizure Sinus¹⁴

Scenario: Ms SS, a 43-year-old female with epilepsy presents with gingival enlargement and bleeding gums. She has been on phenytoin for several years and reports difficulty maintaining oral hygiene

Case 3: Mr Vertigo Veneer¹⁵

Scenario: Mr VV, a 35-year-old male with newly diagnosed epilepsy presents for a check-up. He reports feeling dizzy and having a very dry mouth. He recently started gabapentin

Management:

• Precautions: Assist the patient when getting on and off the dental chair due to dizziness. Educate him on managing dry mouth to reduce caries risk.
• Side Effects Impacting Treatment: Drowsiness, dizziness, ataxia, and tremors can interfere with patient cooperation and the precision of dental procedures.
• Drug Interactions: Be cautious with other CNS depressants (e.g., benzodiazepines for pre-procedure anxiety), especially since the patient has just started the medication. Consider deferring treatment until the patient has stabilized on the new drug.

Parkinson’s Disease¹⁶

• Usually older population
• Characteristics: tremor, difficulty coordinating fine movements, hypokinesia, shuffling gait, skeletal muscle rigidity
• Normal muscle movement: balance muscarinic cholinergic and dopaminergic activities
• Parkinson’s disease: dopaminergic fibres and/or dopamine receptor degenerate
• Rationale tx: provide sx relief
• Pharmacological: dopamine agonists, anticholinergics, MAO-B, others

Drug Classes for Parkinson’s Disease¹⁷

Dopamine agonists

• MOA: stimulate dopamine receptor

• Drug interactions

  • Apomorphine: clarithromycin, erythromycin, fluconazole → prolong QT
  • Bromocriptine + erythromycin: increase ADR
  • Cabergoline + clarithromycin, itraconazole: increase ADR

• ADR

  • Dizziness, drowsiness
  • Orthostatic hypotension
  • Dyskinesia
  • Impulse control disorders

• Headache

• Nasal congestion (can make breathing difficult during treatment)

Impulse Control Disorders

This is a significant psychiatric side effect that can manifest as problem gambling, compulsive shopping, or binge eating (increasing caries risk). Patients may also compulsively commit to expensive cosmetic dental treatments.

Generic name	Brand Name
Apomorphine	Movapo inj
Pramipexole	Sifrol
Rotigotine	Neupro
Ergot derivative
Bromocriptine	Parlodel
Cabergoline	Dostinex

Anticholinergics¹⁸

• MOA: block muscarinic actions of acetylcholine
• Drug interactions
  • Benzatropine, trihexyphenidyl: nil dental interactions
• ADR
  • Dizziness, drowsiness
  • Orthostatic hypotension
  • Dyskinesia
  • Dry mouth

Generic name	Brand Name
Benzatropine	Benztrop
Trihexyphenidyl	Artane

Tertiary amines

• Atropine, Atropine (antidote)
• Benzatropine
• Darifenacin
• Hyoscine hydrobromide
• Orphenadrine
• Oxybutynin
• Solifenacin
• Tolterodine
• Trihexyphenidyl

Quaternary amines

• Glycopyrronium (anaesthesia)
• Hyoscine butylbromide
• Propantheline

Monoamine oxidase inH type B (MAOB inH)¹⁹

• Aka MAOB inH
• MOA: inH MAOB, reduce breakdown of dopamine, may block dopamine re-uptake
• Drug interactions: nil dental interactions
• ADR
  • Orthostatic hypotension
  • Dyskinesia

(involuntary, erratic muscle movements of the face or limbs that can make it challenging for patients to remain still)

Generic name	Brand Name
Rasagiline	Azilect
Safinamide	Xadago
Selegiline	Eldepryl

Other drugs for Parkinson’s²⁰

Note

The lecturer advised students to read up on other drug classes for Parkinson’s disease in their own time.

• Drug interactions: Entacapone + adrenaline: dental relevance?
• Amantadine [ADR]: Orthostatic hypotension, dizziness, dry mouth
• Entacapone [ADR]: Orthostatic hypotension, dry mouth, dyskinesia
• Opicapone [ADR]: Dry mouth, dizziness, dyskinesia
• Combination [ADR]: orthostatic hypotension, dyskinesia, drowsiness, impulse control disorder

Generic name	Brand Name
Amantadine	Symmetrel
Entacapone	Comtan
Levodopa + benserazide	Madopar
Levodopa + carbidopa	Kinson, Sinemet
Levodopa + carbidopa & entacapone	Carlevent, Lecteva
Opicapone	Ongentys

Parkinson’s Disease: Dental Implications²¹

Pharmacological Considerations

• Drug interactions
  • QT prolongation drugs
  • CYP3A4
• ADR
  • [common]: dizziness, drowsiness, orthostatic hypotension, dyskinesia, impulse control disorders, dry mouth

Patient Management¹²

• Orthostatic hypotension
• Fatigue and exhaustion due to disturbed sleep patterns
• Impaired executive functions which leads to distraction and inattention
• Short appointments if possible
• Patient should take levodopa and symptomatic medication 1 hour prior to planned procedure!
• Minimise muscle tone resting jaw opening or possible uncontrolled tremor

Use a bite block and provide frequent breaks to minimize muscle strain.

• Side-effects from medications

Alzheimer’s Disease²²

• A form of dementia
• Characteristics: neuronal cell loss, brain shrinkage, enlarged ventricles, significant histological changes in brain tissue
• Progressive deterioration
• Pathophysiology: neuronal cell death, B-amyloid plaques, neurofibrillary tangles
• Reduction in Ach and raised glutamate?
• Pharmacological: inH acetylcholinesterase, glutamate receptor antagonists

Drug Classes for Alzheimer’s Disease²³

Anticholinesterases

• MOA: decrease breakdown of acetylcholine

Used in early-stage AD, these drugs inhibit the anticholinesterase enzyme, which normally breaks down acetylcholine. This increases the availability and prolongs the action of acetylcholine in the brain.

• Drug interactions [Galantamine]
  • QT prolongation: clarithromycin, erythromycin, fluconazole
  • [CYP3A4 inh]
• ADR
  • Drowsiness, dizziness, tremor, increased sweating, hypertension, fainting

Generic name	Brand Name
Donepezil	Arazil, Aricept
Galantamine	Galantyl, Reminyl
Rivastigmine	Exelon

Other drugs for Alzheimer’s (NMDA Antagonists)²⁴

• MOA: N-methyl-D-aspartate (NMDA) antagonist

In AD, excessive glutamate levels cause overstimulation of NMDA receptors, leading to excessive calcium influx and neuronal damage. Memantine blocks these receptors, preventing this harmful overstimulation.

• Drug interactions: limited information
• ADR
  • [common]: confusion, dizziness, drowsiness, headache, agitation, hallucinations, dyspnoea

Generic name	Brand Name
Memantine	Ebixa, Memanxa

Alzheimer’s Disease: Dental Implications²⁵

• Drug interactions
  • QT prolongation drugs
  • CYP3A4
• ADR
  • [common]: Drowsiness, dizziness, tremor, increased sweating, hypertension, fainting, confusion, headache, agitation, hallucinations, dyspnoea

Patient Factors

• Recognize the patient’s level of cognitive decline.
• A carer or legal representative may be required for informed consent.

Case Studies: Alzheimer’s Disease²⁶

Case 1: Mr Forgetful Fillings

Scenario: Mr. FF, 78, presents for a routine dental check-up. He has early-stage Alzheimer’s and is currently taking galantamine. His medical history also includes hypertension. He reports dizziness and occasional fainting spells

Management:

• Implications of Galantamine: Dizziness and fainting can complicate patient positioning and tolerance of treatment.
• Adrenaline in LA: Use a correct and slow LA technique with negative aspiration. Use the minimum effective dose and monitor the patient closely.
• Drug Interactions: Avoid prescribing CYP3A4 inhibitors like erythromycin or fluconazole if possible.

Case 2: Ms Confused Composite²⁷

Scenario: Ms CC, 81, with moderate Alzheimer’s disease, is on memantine (an NMDA antagonist). She arrives for an extraction and is visibly confused and agitated. Her caregiver reports recent hallucinations

Management:

• Influence of ADRs: Confusion, agitation, and hallucinations can severely complicate communication and patient cooperation.
• Behavioral Strategies: Use calm communication, give clear and simple instructions, schedule shorter appointments, and involve a familiar caregiver to reduce anxiety.
• Consent: Ensure valid consent is obtained, either from the patient if they are deemed capable or from their legal power of attorney.

Psychotropic drugs²⁸

• Major depression
• Anxiety & related disorders
• Eating disorders
• Bipolar disorder
• Insomnia
• ADHD
• Alcohol withdrawal
• Long term treatment for alcohol dependence
• Nicotine dependence
• Opioid dependence

Antidepressants²⁹

Indications

• Major depression
  • Relieve psychological and physical symptoms
  • Improve functional capacity
  • Reduce the likelihood of self-harm or suicide
• Anxiety and related disorders
  • Control symptoms and improve social functioning
• Eating disorders
  • A multidisciplinary approach
  • Psychological treatments [cognitive behaviour therapy, interpersonal psychotherapy, family psychotherapy]
  • SSRIs: bulimia nervosa, binge eating disorder

General Adverse Effects³⁰

• Serotonin toxicity
  • Tramadol
• Withdrawal effects
  • Nausea, vomiting, anxiety, agitation, tremor and many more

Antidepressant Drug Classes³¹

MOA inhibitors

• MOA: Nonselective MAOIs irreversibly inhibit monoamine oxidases A and B
• Drug interactions
  • Serotonin toxicity: tramadol (CI)
  • Adrenaline: may increase effect of adrenaline (caution)
  • Tapentadol: increase risks for HTN (CI)
• ADR [common]
  • Orthostatic hypotension, headache, drowsiness, fatigue, weakness, agitation, tremors, twitching, myoclonus, hyperreflexia, dizziness, dry mouth

(CI) = Contraindicated

Myoclonus: sudden, brief, involuntary muscle jerks or twitches, often described as shock-like movements, that can affect a single muscle or a group of muscles.

SSRIs³²

• MOA: SSRIs selectively inhibit the presynaptic reuptake of serotonin

, increasing its concentration in the synaptic cleft.

• Drug interactions
  • Serotonin toxicity: tramadol
  • Citalopram, escitalopram, fluoxetine + QT prolongation
  • Fluoxetine, fluvoxamine + CYP3A4 inH
• ADR [common]
  • Agitation, drowsiness, tremor, dry mouth, dizziness, headache, sweating, weakness, anxiety

Generic name	Brand Name
Citalopram	Celapram
Escitalopram	Lexapro
Fluoxetine	Zactin
Fluvoxamine	Luvox
Paroxetine	Paxtine
Sertraline	Setrona

Tricyclic antidepressants³³

• MOA: inhibit reuptake of noradrenaline and serotonin into presynaptic terminals
• Drug interactions
  • QT prolongation drugs
  • CNS depressant drugs
  • Adrenaline: added sympathomimetic effects (caution)
  • Clomipramine, imipramine: serotonin toxicity
• ADR [common]
  • Sedation, dry mouth, orthostatic hypotension, tremor, dizziness, sweating, agitation, anxiety, confusion

Generic name	Brand Name
Amitriptyline	Endep
Clomipramine	Anafranil
Dothiepin	Dothep
Doxepin	Deptran
Imipramine	Tofranil
Nortriptyline	Allegron

SNRIs³⁴

• MOA: inH serotonin and noradrenalin reuptake
• Drug interactions
  • Serotonin toxicity
  • Desvenlafaxine + CYP3A4 inH
• ADR
  • [common]: dry mouth, yawning, sweating, dizziness, headache, tremor
  • infrequent: orthostatic hypotension and fainting

Generic name	Brand Name
Desvenlafaxine	Pristiq
Duloxetine	Tixol
Venlafaxine	Efexor

Other Antidepressants³⁵

Generic name (Brand)	Selected drug interaction	Selected ADR
Agomelatine (Valdoxan)	Nil dental	Infrequent (0.1–1%): Anxiety, fatigue, excessive sweating, itch
Mianserin (Lumin)	Nil dental	Common (>1%): Sedation, dry mouth, dizziness, vertigo
Mirtazepine (Axit)	Maybe contribute to serotonin toxicity???	Common (>1%): Sedation, weakness Rare (<0.1%): Orthostatic hypotension, seizures
Moclobemide (Amira)	Serotonin toxicity (tramadol)	Common (>1%): Dry mouth, anxiety, dizziness, headache
Reboxetine (Edronax)	CYP3A4 inH	Common (>1%): Dry mouth, sweating, orthostatic hypotension, headache, paraesthesia, dizziness
Vortioxetine (Brintellix)	Maybe contribute to serotonin toxicity???	Common (>1%): Dry mouth, itch

Antidepressants: Dental implications³⁶

• Drug interactions
  • Adrenaline + TCAs/MAOIs → Risk of hypertensive crisis
  • Tramadol + SSRIs/SNRIs/MAOIs → Risk of serotonin toxicity
  • CYP3A4 inhibitors (e.g. fluoxetine, fluvoxamine, desvenlafaxine) → Affects drug metabolism
• Adverse drug reactions (ADRs)
  • Dry mouth → Increased caries, periodontal risk
  • Drowsiness, dizziness, orthostatic hypotension → Caution with chair positioning, longer procedures
  • Tremors, anxiety, sweating → May affect cooperation
• Patient factors
  • Mental health status: anxiety, depression, withdrawal
  • Long-term therapy → Compliance, oral hygiene challenges
  • Monitor for withdrawal symptoms (esp. with short half-life drugs)

Antipsychotics³⁷

• Indication: acute & chronic psychosis, bipolar disorder

Note

These drugs are used to relieve distressing symptoms like hallucinations, delusions, and severely abnormal thoughts or behaviors. They also have sedative effects that are useful in agitated or aggressive patients.

• MOA: blockade of dopaminergic transmission?
• Drug interactions
  • CNS depressants: check individual monograph
  • QT prolongation: Amisulpride, droperidol, haloperidol, ziprasidone
  • CYP3A4 inH: Aripiprazole, brexpiprazole, cariprazine, haloperidol, lurasidone, quetiapine, ziprasidone
• ADR [common]: sedation, anxiety, agitation, EPSE, orthostatic hypotension, dry mouth
  • EPSE: dystonia, akathisia, parkinsonism, tardive dyskinesia

(abnormal muscle tone affecting facial muscles)

List of Antipsychotics

• Amisulpride
• Aripiprazole
• Asenapine
• Brexpiprazole
• Cariprazine
• Chlorpromazine
• Clozapine
• Droperidol
• Flupentixol
• Haloperidol
• Lurasidone
• Olanzapine
• Paliperidone
• Periciazine
• Quetiapine
• Risperidone
• Ziprasidone
• Zuclopenthixol

Antipsychotics: Dental implications³⁸

• Drug interactions

  • QT prolongation risk, CYP3A4 inhibitors, CNS depression

• Adverse effects relevant to dentistry

  • Dry mouth

• Peripheral edema (especially perioral)

, orthostatic hypotension, sedation, dizziness, agitation, EPSEs

• Patient considerations
  • Assess mental state, ability to consent, and cooperation level
  • Consider increased sensitivity to stress or invasive procedures
  • Evaluate the need for additional support, shorter appointments, or sedation alternatives

Drugs for bipolar disorder³⁹

• Pharmacological
  • Antipsychotics, antiepileptics (carbamazepine, lamotrigine, valproate) – mentioned in antiepileptic lectures
  • Lithium (Lithicarb, Quilonum SR)
• Lithium: [MOA] unknown? Inh dopamine release? Enhance serotonin release?
  • Drug interactions
    • Serotonin toxicity: tramadol
    • NSAIDs: reduce renal lithium excretion

(low-dose aspirin is generally considered safe)

• ADR [common]: metallic taste, fatigue, headache, vertigo, tremor, acne, psoriasis

Bipolar Disorder Drugs: Dental implications⁴⁰

• Lithium interactions
  • Avoid NSAIDs (except low-dose aspirin) → risk of lithium toxicity
  • Monitor for signs of toxicity if analgesics are prescribed
• Serotonin toxicity risk: caution with tramadol
• Common side effects relevant to dentistry
  • Metallic taste → altered taste perception
  • Tremor, fatigue → difficulty with fine motor control, cooperation during procedures
  • Dry skin or acne → consider skin sensitivity around oral cavity
• Communication and care
  • Assess for sedation, mental alertness, and ability to consent
  • Schedule shorter or more frequent appointments if needed

Drugs for anxiety & sleep disorders⁴¹

• Non-pharmacological
  • CBT first line: insomnia & anxiety
  • Remove source of sleep disturbance
  • Sleep hygiene principles
• Pharmacological
  • Benzodiazepines
  • Non-amphetamine psychostimulants
  • Orexin receptor antagonists
  • Other: diphenhydramine, doxylamine, melatonin, zolpidem, zopiclone

Drug Classes for Anxiety & Sleep Disorders⁴²

Benzodiazepines⁸

Warning

Used for short-term relief due to the high risk of dependence.

• MOA: potentiate inhibitory effect of GABA

They target the GABA-A receptor complex, but require the presence of GABA to enhance its inhibitory action, increasing chloride ion influx and causing hyperpolarization.

Warning

Not suitable for long-term antiepileptic therapy due to the development of tolerance.

• Drug interactions
  • Other CNS depressants: monitor sedation
  • Alprazolam: itraconazole, ketoconazole → enhance sedation & respiratory depression
  • Diazepam + fluconazole → increase adverse effect
  • Midazolam + [CYP3A4 inh] → enhance sedation & respiratory depression
• ADR: drowsiness, oversedation, lightheadedness, hypersalivation, ataxia

Ataxia refers to a loss of coordination and balance, resulting in clumsy or awkward movements, often affecting walking, speech, and fine motor skills.

• Alprazolam
• Bromazepam
• Clobazam
• Clonazepam
• Diazepam
• Flunitrazepam
• Lorazepam, Lorazepam (neurology)
• Midazolam (anaesthesia), Midazolam (neurology)
• Nitrazepam
• Oxazepam
• Temazepam

Non-amphetamine psychostimulants⁴³

• MOA: unknown
• Drug interactions
  • CYP3A4 inH
• ADR: dry mouth, headache, anxiety, palpitations, nervousness, dizziness, hypertension

Generic name	Brand Name
Armodafinil	Nuvigil
Modafinil	Modafin

Orexin receptor antagonists⁴⁴

• Indication: chronic insomnia
• MOA: block the binding of wake-promoting orexin A and B neuropeptides
• Drug interactions
  • CYP3A4 inH
• ADR: headache

Generic name	Brand Name
Lemborexant	Dayvigo
Suvorexant	Belsomra

Other⁴⁵

• Drug interactions: other CNS depressants
• Sedating antihistamines: diphenhydramine, doxylamine
  • ADR: sedation, psychomotor impairment, dizziness, confusion, headache, dry mouth
• Melatonin: control of circadian rhythms
  • ADR: nil dental
• GABA agonists: zolpidem, zopiclone
  • [Zopiclone] ADR: taste disturbance (bitter), dry mouth, drowsiness, impaired alertness the next morning

Many of these drugs can cause a bad taste.

Generic name	Brand Name
Melatonin	Circadin
Zolpidem	Stilnox
Zopiclone	Imrest

Anxiety & Sleep Disorder Drugs: Dental implications⁴⁶

• Sedation & CNS depression: increased risk with benzodiazepines, antihistamines, GABA agonists
• Cognitive/psychomotor impairment: affects alertness and safety, especially with sedating antihistamines
• Dry mouth: common; raises risk of caries and mucosal issues
• Taste disturbance: noted with zopiclone
• Headache & anxiety: possible with orexin antagonists and psychostimulants
• Management: schedule when alert, avoid CNS depressants, emphasize oral hygiene, clear aftercare instructions

Drugs for attention deficit hyperactivity disorder (ADHD)⁴⁷

• Chronic condition: inattentive, hyperactive-impulsive, combination
• Pharmacological
  • Drug choice: psychostimulants
  • Other: Atomoxetine, guanfacine or clonidine
• Lack of evidence
  • Dietary replacement
  • Supplementation of selected vitamins
  • Biofeedback
  • Perceptual stimulation

Drug Classes for ADHD⁴⁸

Psychostimulants

• MOA: enhance dopaminergic and noradrenergic neurotransmission
• Drug interactions: Nil dental
• ADR
  • [common]: dry mouth, anxiety, irritability, headache, dizziness, aggression, palpitations
  • Infrequent: movement disorders, tics

Generic name	Brand Name
Dexamfetamine	Dexamfetamine
Lisdexamfetamine	Vyvanse
Methylphenidate	Concerta

Other⁴⁵

• Atomoxetine: selectively inhibits presynaptic noradrenaline reuptake
  • Drug interactions: nil dental
  • ADR [common]: dry mouth, dizziness, irritability, aggression, temper tantrums
  • ADR infrequent: palpitations, orthostatic hypotension
• Guanfacine: selective alpha₂ₐ adrenoreceptor agonist
  • Drug interactions: CNS depressant, CYP3A4 inH
  • ADR [common]: drowsiness, dizziness, dry mouth, headache, hypotension, fatigue, sedation
  • ADR infrequent: fainting

Generic name	Brand Name
Atomoxetine	Atomoxetine
Guanfacine	Intuniv

ADHD Drugs: Dental implications⁴⁹

• Psychostimulants (dexamfetamine, methylphenidate, lisdexamfetamine)
  • ADR: dry mouth, anxiety, irritability, headache, palpitations, movement disorders (rare)
  • Drug interactions: none significant in dentistry
• Atomoxetine
  • ADR: dry mouth, dizziness, irritability, aggression, temper tantrums, palpitations (rare)
  • Drug interactions: none significant in dentistry
• Guanfacine
  • ADR: drowsiness, dry mouth, dizziness, hypotension, sedation, fainting (rare)
  • Drug interactions: CNS depressants, CYP3A4 inhibitors

Drugs for Substance Dependence⁵⁰

Alcohol Dependence

• Alcohol withdrawal sx: CNS depressants (benzodiazepines)
  • Symptomatic tx: analgesics, antiemetics, antipsychotics (severe agitation & hallucination)
• Long term tx for alcohol dependence
  • Support ongoing abstinence from alcohol.
  • Decrease alcohol intake where abstinence is not achieved.
  • Minimise social, physical and psychological consequences.
• Drug choice
  • Acamprosate: MOA unclear, nil ADR in dental
  • Naltrexone: [ADR] transient, subsides after 1-2wks, interact w/ opioids
  • Disulfiram: [ADR] drowsiness, headache, avoid metronidazole

Nicotine Dependence⁵¹

• Nicotine: CNS stimulant → feelings of pleasure, relief of anxiety etc
  • Smoking cessation: unpleasant withdrawals
• Non-drug treatment: counselling, behavioural techniques, encouragement and support
• Drug choice
  • Bupropion: MOA unclear, [ADR] dry mouth, dizziness, agitation, anxiety, tremor, headache
  • NRT: [ADR] dizziness, headache, burning-lip sensation (mouth spray), hiccups, cough (inhalation), vivid dreams (especially 24-hour patch)
  • Varenicline: [ADR] headache, taste disturbance, abnormal dreams, sleep disorder

Opioid Dependence⁵²

• Chronic, frequently relapsing illness
  • Opioids produce euphoric effects but tolerance develops rapidly
• Withdrawals symptoms: extreme anxiety, restlessness, insomnia, nausea, unpleasant but not life threatening
• Drug choice
  • Buprenorphine: [ADR] not dental related, interaction (opioids, ketoconazole)
  • Methadone: [interaction] QT prolongation
  • Naltrexone: already mentioned

Dental Implications of Substance Abuse⁵³

Substance of abuse	Dental implications
Cannabis	• Poor oral and periodontal health • Acute dose + LA w/ adrenaline may prolong tachycardia • Chronic smokers: oral leucoplakia, oral cancer, oral candidiasis
Methamphetamine	• Poor OH, rampant caries • Bruxism, clenching, non-carious tooth wear • Xerostomia • LA w/ vasoconstrictor avoid when patient is intoxicated
Cocaine	• Bruxism, clenching, non-carious tooth wear • Gingival erosions, retraction, ulceration
Opioids	• Rampant caries, periodontitis • Anxiety • Injectables → risks blood borne viruses & infective endocarditis

Note on Moclobemide

Moclobemide (a reversible MAOI) can interact with sympathomimetic agents like adrenaline.

General Dental Implications for Dependence⁵⁴

• Poor diet & oral hygiene worsen oral health
• Smoking increases risk of oral cancer
• Watch for “doctor shoppers” requesting analgesics/anxiolytics

Be suspicious of patients who seem overly knowledgeable about specific drugs or brands. It is acceptable to refuse to prescribe when in doubt.

• Know drug preferences & risks; refuse supply if unsure
• Multiple drug use common: cannabis, methamphetamine, cocaine, opioids
• Coordinate care with other healthcare providers for safe management

Case Studies: Psychotropics⁵⁵

Case 1: Major Depression

Scenario: 45-year-old female on sertraline (SSRI) for major depression presents for routine dental extraction. She complains of dry mouth and occasional dizziness

Management:

• SSRIs commonly cause dry mouth and initial dizziness. Watch for serotonin toxicity if considering tramadol. If the patient is non-compliant with her medication, advise her to see her GP.

Case 2: Schizophrenia⁵⁶

Scenario: 32-year-old male on haloperidol for schizophrenia complains of dry mouth and tremors; requires scaling and root planning

Management:

• Haloperidol can cause dry mouth, sedation, orthostatic hypotension, and extrapyramidal side effects (EPS) like tremor, which can impair oral hygiene. Monitor for QT prolongation and be cautious with CYP3A4 inhibitors.

Case 3: Bipolar Disorder⁵⁷

Scenario: 40-year-old male on lithium therapy presents for dental implant surgery. He reports metallic taste and mild tremor

Management:

• Metallic taste and tremor are common with lithium. NSAIDs must be used with extreme caution as they can increase lithium levels and cause toxicity.

Case 4: Anxiety & Sleep Disorders⁵⁸

Scenario: 28-year-old female on diazepam for short term relief of anxiety requests extraction due to painful tooth

Management:

• Diazepam causes sedation and dizziness. It can also cause dry mouth or hypersalivation (drooling), which can interfere with restorative work. Avoid co-administration with other CNS depressants.

Case 5: ADHD⁵⁹

Scenario: 15-year-old male treated with methylphenidate for ADHD has dental caries and complains of dry mouth

Management:

• Psychostimulants commonly cause dry mouth, increasing caries risk. There are no major drug interactions of concern for dentists. Management involves meticulous oral hygiene education, regular recalls, and fluoride treatments.

Case 6: Substance Dependence Treatment⁶⁰

Scenario: 38-year-old male in methadone maintenance therapy for opioid dependence complains of rampant caries and poor oral health

Management:

• Patients on methadone often have high rates of caries and periodontal disease. For pain management, avoid prescribing opioids to prevent relapse; use non-opioid analgesics instead. Be cautious with other CNS depressants and drugs that prolong the QT interval.

References⁶¹

• Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. Rang & Dale’s pharmacology. 10th ed. Edinburgh: Elsevier; 2023
• Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd; 2000. Psychotropics; [updated 2025; cited 2025]. Available from: UWA Onesearch
• Pharmaceutical Society of Australia. Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021
• Ali K. Clinical dental pharmacology. 1st ed. Oxford: Wiley-Blackwell; 2023
• Bullock S, Manias E. Fundamentals of pharmacology. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017
• MIMS Australia. eMIMSelite: Consumer medicine information, specific clinical monograph [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch

Footnotes

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