HANDOUT 16: o Suicidality: recurrent thoughts of death,

Antidepressants, Antipsychotics, and suicidal ideation, suicidal plan, suicide

Mood Stabilizers
What is Depression?
 Common mental disorder
 Presents with (WHO definition):
o depressed mood
o loss of interest or pleasure
o feelings of guilt or low self-worth
o disturbed sleep or appetite
o low energy
o poor concentration
 Lacking of neurotransmitters:
o Norepinephrine
o Serotonin
o Dopamine
Types of Depression
1. Reactive or Secondary Depression
 AKA “Exogenous Depression”
 Occurring in response to real stimuli such as
grief, illness, & life crisis events.
 Normal na nangyayari in people
2. Endogenous Depression or Major Depressive
Disorder (MDD)
 Genetically determined
 A mental disorder characterized by an all-
encompassing low mood accompanied by
low self-esteem, and by loss of interest or
pleasure in normally enjoyable activities.
3. Depression associated with Bipolar Affective
(Manic-Depressive) Disorder
 Highly elated – manic
 Low mood – depressive
attempt
 Criteria:
o 5 (or more) of the symptoms are present
during the same 2-week period
o At least one of the symptoms is either (1)
depressed mood or (2) loss of interest or
pleasure.
What are antidepressants?
 AKA “Thymoleptics”
 They increase the activity of neurotransmitters in the
brain.
 Antidepressants Inhibit reuptake
Serotonin Synthesis
 Essential amino acid L-tryptophan is hydrolyzed
(essential  must come from the diet; tryptophan-rich
foods  dairy products, peanuts, bananas)
o Hydroxylation is the rate-limiting step of
serotonin synthesis
o Can be blocked by certain agents like p-
chloro-phenylalanine (PCPA; Fenclonine) and
p-chloroamphetamine
 Followed by decarboxylation
 After synthesis, 5-HT is then stored or
inactivated/degraded by MAO via oxidation (5-HT 
5-hydroxytryptamine)

Major Depressive Episodes Criteria

 Symptoms:
o Mood: depressed mood most of the day,  Melatonin – hormone secreted by the pineal gland; for
nearly everyday sleeping rhythm
o Sleep: Insomnia or hypersomnia (tulog nang
tulog) Serotonin Transmission
o Interest: marked decrease in interest and
pleasure in most activities
o Guilt: feelings of worthlessness or
inappropriate guilt
o Energy: fatigue or low energy nearly
everyday
o Concentration: decreased concentration or
increased indecisiveness
o Appetite: increased or decreased appetite or
weight gain or loss
o Psychomotor: psychomotor agitation or
 Fates of serotonin: 1) can go to the receptors, 2) can be
retardation
reuptaken by the SERT (less 5-HT in synapse), 3)
degradation
  Sertraline
 Paroxetine
 Escitalopram*
 MOA: Inhibition of SERT; little inhibition of
NET
4. Dual Serotonin and Norepinephrine Reuptake
Inhibitor (SNRI)
 Venlafaxine*
 Duloxetine*
 Milnacipran
 Desvenlafaxine
 MOA: Moderate selective blockade of NET
 Fates of NE: 1) bind to adrenoceptors (a, b, dopamine), and SERT
2) reuptaken by NET  less NE in synapse = depression 5. Serotonin-2 Antagonist and Reuptake Inhibitors
 First catecholamine to be synthesized is dopamine, (SARIs)
followed by NE  Nefazodone
 DAT – dopamine transporter, prevents reuptake of  Trazodone
dopamine  MOA: Nefazodone blocks SERT weakly
6. Norepinephrine and Dopamine Reuptake Inhibitor
Available Antidepressants (NDRI)
1. Tricyclics and Tetracyclics (TCA)  Bupropion (also for smoking cessation)
 Imipramine*  MOA: Mixed blockade of NET and DAT
 Doxepin 7. Noradrenergic and Specific Serotonergic Anti-
 Desipramine* depressant (NaSSAs)
 Amoxepine  Mirtazapine
 Trimipramine  MOA: Mixed blockade of NET and SERT; α2
 Maprotiline antagonist
 Clomipramine 8. Noradrenaline Specific Reuptake Inhibitor (NRI)
 Amitriptyline*  Reboxetine
 Nortriptyline*  MOA: Blockade of NET
 Protriptyline
 MOA: Mixed blockade of NET and SERT Other Uses of Antidepressants
2. Monoamine Oxidase Inhibitors (MAOIs)  Panic Disorder
 Tranylcypromine and Phenelzine – both o Imipramine
MAO-A and MAO-B inhibitors) o MAO Inhibitors & Benzodiazepines
 Selegiline – MAO-B inhibitor at low dose, o SSRI
MAO-A inhibitor at high doses; newly  Obsessive-Compulsive Disorder
discovered; also used in Parkinson’s disease o SSRI
 Moclobemide – not available in the USA,  Enuresis (urinary incontinence)
MAO-A Inhibitor o TCA
 Isocarboxazid – Both MAO-A and MAO-B  Chronic Pain
inhibitor o TCA
 MOA: Inhibition of MAO o Venlafaxine
o NOTE: Hydrazine derivatives: Phenelzine o Duloxetine
and Isocarboxazid  Eating Disorder (Bulimia – forced vomiting)
 Reversible: Moclobemide; reversible meaning o Fluoxetine
pwede pa siya matanggal kay MAO  Attention Deficit Hyperkinetic Disorder (ADHD)
 Non-reversible: Hydrazine derivatives, o Atomoxetine (SSRI)
Tranylcypromine, Selegiline o DOC: Methylphenidate (Ritalin)
o Tranylcypromine closely resembles  Social Phobia
Dextroamphetamine (stimulant) o SSRI
3. Serotonin Selective Reuptake Inhibitors (SSRIs)  Generalized Anxiety Disorder
 Fluoxetine o SNRI
 Fluvoxamine
 Citalopram*
St. John’s Wort o Enhanced elimination. Repeat-dose
 Hypericum perforatum (Hypericaceae) charcoal are not effective.
 The plant is named for Saint John the Baptist because
its bright yellow flowers bloom around the time of his Antipsychotics / Neuroleptics
birth in June. Psychosis
 Contains hypericin, a chemical that reportedly has  a mental illness in which a person loses contact with
anti-inflammatory and antidepressant properties. reality and has difficulty functioning in daily life.
 Also hyperforin (Antidepressant also) Schizophrenia
 a form of psychosis
Mechanism of Toxicity and Clinical Presentation Antipsychotic Drugs
 Most agents cause CNS depression. Bupropion can  AKA neuroleptics
also cause seizures.  Used in Schizophrenia and other psychoses (Multiple
 Trazodone produces peripheral alpha-adrenergic personality disorder, bipolar disorder)
blockade, which can result in hypotension and  Reserpine and Chlorpromazine were the first to be
priapism. used but Reserpine is no longer used.
 Severe rigidity and hyperthermia = MAOIs +  Schizophrenia is not cured by drug therapy, but the
Meperidine (Demerol), Dextromethorphan, Fluoxetine symptoms may be ameliorated by antipsychotic
(Prozac), Paroxetine (Paxil), Sertraline (Zoloft) or drugs.
Tryptophan  Unfortunately, protracted therapy (years) is often
 Hypertensive Crisis = MAOIs + Tyramine-containing needed and can result in severe toxicity in some
foods (foods that underwent fermentation) patients.
o NOTE: MAOIs decrease the breakdown of
tyramine from ingested food, thus increasing Pathophysiology of Schizophrenia
the level of tyramine in the body. A. Genetic Theories
 Serotonin syndrome = Serotonin uptake inhibitors + B. Neurophysiological Theories
MAOIs or ingestion of tryptophan  Dopamine Hypothesis – Increased Dopamine;
o Characterized by: decreased dopamine – Parkinson’s disease
 Confusion  Serotonin Hypothesis – Increased Serotonin
 Hypomania  Glutamate Hypothesis – Hypofunction of NMDA
 Restlessness receptor
 Myoclonus C. Psychosocial Theories
 Hyperreflexia  stress
 Diaphoresis  lack of interpersonal skills
 Shivering  conflicting and contradictory family communication
 Tremor  socioeconomic influences
 Incoordination
 Hyperthermia* Clinical Features of Schizophrenia
 Positive Symptoms
Treatment o Hallucinations
A. Emergency and supportive measure o Delusions
B. Specific drugs and antidotes. o Thought Disorders
 For serotonin syndrome, reports claim benefit from: o Disorganized Speech
o Methylsergide (Sansert), 2 mg orally every 6 o Bizarre Behavior
hrs for 3 doses o Insomnia
 Drug for migraine o Combativeness
o Cyproheptadine (Periactin), 4 mg orally every
hour for 3 doses Delusion Hallucination
 1st gen antihistamine - False belief that have no - False perceptions in the
 For MAOIs intoxication, alpha-adrenergic blockers or basis in reality. absence of any relevant
combined alpha-and beta-adrenergic blockers are sensory stimulus.
particularly useful.  Grandiose (ex. feel  Auditory – most
C. Decontamination mo ikaw smartest) common
1. Prehospital. Administer activated charcoal and ipecac-  Referential (ex. feel  Visual – less
mo ikaw pinag common
induced emesis for initial treatment.
uusapan)  Olfactory – rare
2. Hospital. Administer activated charcoal and cathartic.
 Tactile
  Persecutory (ex. feel o Chlorpromazine, Promazine,
mo ikaw may Triflupromazine
kasalanan)  Piperidine
 Sexual (ex. feel mo o Thioridazine, Mesoridazine
may sexual desire  Piperazine
sayo) o Trifluoperazine, Perphenazine,
 Nihilistic - the
Fluphenazine, Perphenazine,
general rejection of
Prochlorperazine
established social
2. Thioxanthene Derivatives (“Thixene or Thixol”)
conventions and
beliefs, especially of  Thiothixene
morality and 3. Butyrophenone Derivatives (“Peridol”)
religion  Haloperidol
NOTE: Prochlorperazine – an antipsychotic with anti-emetic
 Negative Symptoms property
o Affective flattening – unable to show
emotional expression Potency with Traditional Neuroleptics
o Alogia – no verbal output, can speak but  Butyrophenones = Piperazine > Piperidine > or equal
does not want to respond to Thioxanthene >> Alipathic
o Apathy – inability to relate in highly  Example: Haloperidol = Fluphenazine
emotional situation  Explanation: butyrophenones have the same potency of
o Amotivation piperazine, mas potetnt si piperazine kaysa piperidine,
o Anhedonia – unable to derive pleasure from piperidine has greater or equal potency to
previously enjoyed activity thioxanthene, thioxanthene has 2x greater potency
o Avolition – no voluntary activity than alipathic
o Asocial behavior
o Inattentiveness Significance of Potency Rank
 The more potent = The more risky
Antipsychotic Agents  Example:
1. Typical or Traditional/Older Agents – primarily o Risk of EPS = more potent
block D2 receptors o Risk of NMS = more potent (Tx: Dantrolene)
 Phenothiazines* NOTE: Depot antipsychotics have common salt of “decanoate”
 Thioxanthenes* (IM Depot) that increases duration of action (2 weeks to 1
 Butyrophenones* month).
 Molindone  Depot antipsychotics = hindi madalas ang
 Pimozide administration, because matagal ang DOA
2. Atypical/Newer/2nd Generation Agents – block  Haloperidol decanoate is given every month.
D4/2/3 and 5-HT receptors  Fluphenazine decanoate is given every 14 days
 Resperidone (“Fortnightly Administration”)
 Olanzapine
 Quetiapine Adverse Effects of Antipsychotic Agents
 Clozapine  Extrapyramidal Symptoms (EPS)
 Ziprasidone o Akathisia
 Loxapine  Most common, involuntary
 Cariprazine repetitive movements of hands and
 Aripiprazole and Amisulpride (are not feet
associated with weight gain)  Empiric Treatment: Benzodiazepines
3. Glutamatergic Agents – still in later clinical trials o Parkinson-like/pseudo parkinsonism
 Bitopertin – for negative symptoms  Tremors, rigidity, Akinesia, and
 Sarcoserine – for both positive and negative Postural instability
symptoms  Akinesia – absence of
movement
Classes of Antipsychotic Agents  Treatment: Anticholinergics
1. Phenothiazine Derivatives (“Promazine”) (Biperiden, Benztropine,
 Aliphatic Trihexyphenidyl, Diphenhydramine)
 o Dystonia  Respiratory arrest
 Abnormal muscle tone  Hypothermia
 Treatment: Anticholinergics  Hypotension
 NOTE: Acute Dystonia Crisis – DOC C. Chronic anti-psychotic medication may develop:
is Diphenhydramine IV  Neuroleptic malignant syndrome (NMS)
 Seizures  Rigidity
 Metabolic & Endocrine Effects  Hyperthermia
o Weight gain  Sweating
 especially by Clozapine &  Lactic acidosis
Olanzapine  Rhabdomyolysis
 except Aripiprazole and Amisulpride
o Hyperglycemia Treatment
 especially by Olanzapine A. Emergency and supportive measures
 less by Aripiprazole and Ziprasidone B. Specific drugs and antidotes. There is no specific antidote.
o In women 1. For dystonia, give diphenhydramine, 0.5-1 mg/kg IM
 Hyperprolactinemia and infertility or IV.
 Hyperprolactinemia – 2. For cardiotoxic effects, treat with bicarbonate, 1-
excessive breastmilk 2meq/kg IV.
o In men C. Decontamination
 loss of libido and impotence (less 1. Prehospital. Ipecac-induced emesis may be useful for
by Aripiprazole and Ziprasidone) initial treatment.
 Aripiprazole (Abilify®) 2. Hospital. Administer activated charcoal and cathartic.
 Ocular Complications D. Enhanced elimination. None.
o Deposits in the cornea & lens
 by Chlorpromazine Mood-Stabilizing Drugs / Mood Stabilizer
o Retinal deposits Bipolar Affective Disorder
 by Thioridazine  Presence of one or more episodes of abnormally
 Cardiac Toxicity elevated energy levels, cognition, and mood
o QT Prolongation  Treatment:
 especially by Thioridazine o Lithium has been the mainstay of treatment
 Ziprasidone carries great risk of QT for many years.
prolongation o Newer antipsychotic agents and several
 Neuroleptic Malignant Syndrome (NMS) antiseizure drugs.
o Hyperthermia Bipolar Disorder
o Altered consciousness  Aka “Bipolar Affective Disorder”, “Manic-Depressive
o Autonomic changes Disorder”, “Manic Depression”
 tachycardia  When manic:
 unstable blood pressure o feel intensely elated, self-important,
o Managed with dantrolene or bromocriptine energetic, and irritable
o milder form is hypomania
Clinical Presentation of Toxicity  When depressed:
A. Mild intoxication causes: o experience painful sadness, negative
 Sedation thinking, and indifference to things that used
 Small pupils to bring happiness.
 Orthostatic hypotension
 REPORTS: Neutropenia (low neutrophils) by Mood Stabilizing Drugs
acute ingestion of chlorpromazine 1. Lithium
 Anticholinergic manifestations include:  Common salt is carbonate.
o Dry mouth  MOA is uncertain.
o Absence of sweating  Has effects on:
o Tachycardia o electrolytes (since Lithium is a cation)
o Urinary retention o neurotransmitters and their release
B. Severe intoxication may cause: o second messengers
 Coma o intracellular enzymes
 Seizures
  Adverse Effects & Complications: Clinical Presentation of Lithium
o Neurologic Adverse Effects  Mild to moderate intoxication:
 Tremor o Lethargy
o Effects on Thyroid Functions o Muscular weakness
 Decreases thyroid function o Slurred speech
o Edema o Ataxia
 Associated with sodium retention o Tremor
o Cardiac Adverse Effects o Rigidity
 Bradycardia-Tachycardia (Sick- o Extrapyramidal effects
Sinus) Syndrome  Severe intoxications:
Lithium further depresses the o Delirium
sinus node. o Coma
T wave flattening is often o Convulsions
observed on the ECG. o Hyperthermia
o Use during pregnancy
 Ebstein Anomaly Treatment
A congenital cardiac anomaly A. Emergency and supportive measures
in newborns B. Specific drugs and antidotes. There is no specific antidote.
o Misc. adverse effects  Thiazide diuretics and indomethacin have been used
 Transient acneiform eruptions for the treatment of nephrogenic diabetes insipidus.
2. Valproic Acid C. Decontamination
 An antiepileptic drug  Prehospital: Ipecac-induced emesis may be useful for
 Recognized as first-line treatment for acute initial treatment.
mania.  Hospital: Induce emesis or perform gastric lavage.
 MOA is unclear. Whole bowel irrigation may enhance gut
 Toxicity: nausea, vomiting, and other decontamination.
gastrointestinal complaints such as D. Enhanced elimination: Hemodialysis, Forced diuresis.
abdominal pain and heartburn
3. Carbamazepine
 Closely related to imipramine (a TCA)
 Anti-epileptic
 Used for acute mania and prophylaxis in
depressive phase
 MOA is unclear.
 Blood dyscrasias is the prominent adverse
effect.
 Toxicity symptoms are: diplopia and ataxia.
o NOTE: Ataxia is lack of voluntary
coordination of muscle movements.
o Diplopia – double vision
4. Lamotrigine
 Used for acute mania and prophylaxis in
depressive phase
 MOA is unclear.
 causes Stevens-Johnson syndrome (SJS)
o a very rare but potentially fatal skin
condition

Toxic Dose of Lithium

 Acute ingestion of more than 20-30 tablets by an
adult would potentially cause serious toxicity.
 Nephrogenic diabetes insipidus is a recognized
complication of chronic lithium therapy.
o DI: lack of anti-diuretic hormone