Schizophrenia, Bipolar, ADHD, Pain, and Substance Use Disorders: Key Concepts and Treatments

Positive Symptoms

Hallucinations, delusions, disorganized speech treated by both First-Generation (FGAs) and Second-Generation Antipsychotics (SGAs).

Negative Symptoms

Flat affect, anhedonia, avolition; SGAs are generally preferred and more effective than FGAs.

Cognitive Symptoms

Impaired attention and memory; very difficult to treat; SGAs may offer slight benefits over FGAs.

Mesolimbic Pathway

Hyperactivity causes Positive symptoms; antagonism here treats symptoms.

Mesocortical Pathway

Hypoactivity causes Negative/Cognitive symptoms.

Nigrostriatal Pathway

Antagonism here causes Extrapyramidal Symptoms (EPS).

Tuberoinfundibular Pathway

Antagonism here causes Hyperprolactinemia (galactorrhea, amenorrhea, gynecomastia).

Black Box Warnings (BBWs)

All antipsychotics: Increased risk of mortality in elderly patients with dementia-related psychosis.

Clozapine Specific BBWs

Severe neutropenia (agranulocytosis), orthostatic hypotension/bradycardia/syncope, seizures, myocarditis/cardiomyopathy.

First-Generation Antipsychotics (FGAs)

Primarily strong dopamine (D2) antagonists with a higher risk of EPS and hyperprolactinemia.

Second-Generation Antipsychotics (SGAs)

Serotonin (5-HT2A) and moderate Dopamine (D2) antagonists with a lower risk of EPS.

B52 Cocktail

Haloperidol 5mg + Lorazepam 2mg + Diphenhydramine 50mg (or Benztropine) given IM to prevent EPS.

Clozapine Therapy

Used for treatment-resistant schizophrenia; requires monitoring of Absolute Neutrophil Count (ANC).

Clozapine Monitoring

ANC must be ≥ 1500/mm³ to start; checked weekly for 6 months, then every 4 weeks thereafter.

Acute Dystonia

Severe muscle spasms (neck, eyes); treated with IM anticholinergics (Benztropine, Diphenhydramine).

Akathisia

Severe inner restlessness/pacing; treated with beta-blockers (Propranolol) or dose reduction.

Pseudoparkinsonism

Tremor, rigidity, bradykinesia; treated with anticholinergics (Benztropine, Trihexyphenidyl) or Amantadine.

Tardive Dyskinesia (TD)

Involuntary facial/tongue movements; treatment includes stopping the drug or switching to Clozapine.

Lithium Toxicity

Symptoms include coarse tremor, vomiting, diarrhea, confusion, ataxia; action includes holding the dose and hydration.

Lithium Therapeutic Range

0.6 - 1.2 mEq/L; draw trough level 12 hours post-dose.

Valproate Therapeutic Range

50 - 125 mcg/mL.

Carbamazepine Therapeutic Range

4 - 12 mcg/mL.

Methylphenidate-based Stimulants

Includes Ritalin, Concerta, Daytrana, Focalin (dexmethylphenidate).

Amphetamine-based Stimulants

Includes Adderall (mixed amphetamine salts), Vyvanse (lisdexamfetamine), Dexedrine.

Atomoxetine (Strattera)

SNRI; takes 2-4 weeks to work; preferred if there is a substance abuse history in the home.

Guanfacine (Intuniv) & Clonidine (Kapvay)

Alpha-2 agonists; good for hyperactivity/impulsivity and addressing sleep issues.

Consequences of not treating

Increased risk of poor academic performance, injuries/accidents, poor self-esteem, and later development of Substance Use Disorders (SUDs).

Black Box Warnings for Stimulants

High potential for abuse and dependence.

Black Box Warnings for Atomoxetine

Increased risk of suicidal ideation in children/adolescents.

Lisdexamfetamine (Vyvanse)

It is a prodrug that requires cleavage by red blood cells in the GI tract to become active dextroamphetamine. It cannot be crushed and snorted or injected to achieve a 'rush.'

Daytrana

Methylphenidate transdermal patch (apply to hip, remove after 9 hours).

Concerta

OROS technology. Leaves a 'ghost tablet' in the stool.

Chewables/Liquids for ADHD

Quillichew, Dyanavel XR, Quillivant XR (good for kids who can't swallow pills).

Tolerance

Needing a higher dose to achieve the same pain relief.

Cross-tolerance

Incomplete tolerance across different opioids; when switching opioids, you must reduce the equianalgesic dose by 25-50% to prevent overdose.

Pseudoaddiction

Drug-seeking behaviors caused by undertreated pain. Behaviors resolve when pain is adequately managed.

WHO Pain Ladder - Mild Pain

Non-opioid (APAP, NSAID) ± adjuvant.

WHO Pain Ladder - Moderate Pain

Weak opioid (Codeine, Tramadol) ± non-opioid ± adjuvant.

WHO Pain Ladder - Severe Pain

Strong opioid (Morphine, Fentanyl) ± non-opioid ± adjuvant.

Suzetrigine (Mechanism)

It is a highly selective NaV1.8 voltage-gated sodium channel inhibitor, working peripherally to stop pain signaling without the central nervous system side effects of opioids.

CYP2D6

Converts Codeine to active morphine, and Tramadol to its active metabolite (O-desmethyltramadol).

Poor metabolizers

Get no pain relief; Ultra-rapid metabolizers are at high risk for fatal respiratory depression.

Adjuvant Treatments for Neuropathic Pain

TCAs/SNRIs/Gabapentin: Excellent for neuropathic (nerve) pain.

Addictive Muscle Relaxants

Carisoprodol (Soma) - Schedule IV.

Non-addictive Muscle Relaxants

Cyclobenzaprine, Baclofen, Tizanidine, Methocarbamol.

Ceiling Effects of APAP

APAP (Acetaminophen) has a ceiling effect for analgesia and a strict daily limit (max 4,000 mg/day) due to severe hepatotoxicity.

Opiate Origins

Natural: Morphine, Codeine; Semi-synthetic: Hydrocodone, Oxycodone, Hydromorphone; Synthetic: Fentanyl, Methadone; Partial Agonists: Buprenorphine.

Opioid Schedules

Most strong opioids are CII. Buprenorphine is CIII. Tramadol is CIV.

Tolerance to Side Effects

Patients build tolerance to sedation and nausea, but NEVER build tolerance to constipation.

Opioid Constipation Treatment

Must use a stimulant laxative (Senna or Bisacodyl), often with a stool softener (Docusate). 'Mush and push.'

Age Limits for Codeine and Tramadol

Contraindicated in children <12 years old, and <18 years old following tonsillectomy/adenoidectomy.

Allergies to Opioids

True allergies are rare. If a patient is allergic to the phenanthrene class (Morphine, Codeine, Oxy/Hydrocodone), switch to a different chemical class like phenylpiperidines (Fentanyl) or diphenylheptanes (Methadone).

Fentanyl Patches

Changed every 72 hours (sometimes 48h in rapid metabolizers). Takes 12-24 hours to reach full therapeutic blood levels.

Naloxone

Opioid antagonist. Added to oral pills (like Suboxone or Targiniq) as a deterrent; it is poorly absorbed orally but immediately induces withdrawal if the pill is crushed and injected.

Alcohol as Most Abused Drug

Alcohol is the most widely used and abused substance by Americans.

Withdrawal Symptoms for Alcohol & Benzodiazepines

Life-threatening (seizures, delirium tremens, tachycardia). Detox protocol: Tapering with Benzodiazepines (e.g., Lorazepam, Chlordiazepoxide).

Withdrawal Symptoms for Opiates

Flu-like, diarrhea, yawning, severe muscle aches, pupil dilation (miserable, but generally not life-threatening). Detox protocol: Buprenorphine, Methadone, or Clonidine.

Withdrawal Symptoms for Stimulants

Severe fatigue, increased appetite, deep depression ('crash').

Rally Pack / Banana Bag

Contains IV Fluids + Thiamine (B1) + Folic Acid + Multivitamins + Magnesium to correct nutritional deficiencies in alcoholics.

Abusable OTCs

Dextromethorphan (DXM) in high doses ('robotripping'), Loperamide (Imodium) in massive doses, Pseudoephedrine (used to make meth).

Blood Alcohol Content (BAC)

Move the decimal point two places to the right. A BAC of 0.08% is equal to 80 mg/dL.

Addiction Treatment Models - Abstinence Model

Complete cessation with Disulfiram (Antabuse), Acamprosate (Campral), Naltrexone (Vivitrol/Revia).

Addiction Treatment Models - Harm-Reduction Model

Minimizing danger and illicit drug use with Methadone and Buprenorphine.

Methadone Legalities

For Addiction Detox/Maintenance: Can only be dispensed by an FDA/DEA-registered Opioid Treatment Program (OTP/Methadone clinic). For Pain: Can be dispensed at a regular retail pharmacy.

Overdose Antidotes for Opiates

Naloxone (Narcan).

Overdose Antidotes for Benzodiazepines

Flumazenil (Romazicon) — Note: high risk of triggering seizures.

Zyban (Bupropion)

Start 1-2 weeks before quit date. Contraindicated in patients with a history of seizures or eating disorders.

Chantix (Varenicline)

Start 1 week before quit date. Should NOT be used with nicotine products.