PSYCHOPHARMACOLOGY

Ethel Maureen B. Pagaddu, MD

Cagayan Valley Medical Center
• Psychopharmacology is a science dedicated in
part to discovering where molecular lesions exist
in the nervous system in order to determine what
is wrong with chemical neurotransmission.

• Knowledge of the molecular problem that leads

to abnormal neurotransmission can generate a
rationale for developing a drug therapy to correct
it, thereby removing the psychiatric and
neurological symptoms of the brain disorder.
• The clinical effects of drugs are best
understood in terms of
– Pharmacokinetics : which describes what the
body does to a drug
– Pharmacodynamics : which describes what the
drug does to the body
• time course and intensity of a drug's effects are
referred to as its pharmacodynamics
• include receptor mechanisms, the dose-response
curve, the therapeutic index, and the development of
tolerance, dependence, and withdrawal phenomena
• drug mechanism of action
• Side Effects
– unavoidable risk of medication treatment
– prescribing clinicians should be familiar with the
more common adverse effects, as well as those
with serious medical consequences
– include the probability of its occurrence, its
impact on a patient's quality of life, its time
course, and its cause
• Therapeutic Index
– a relative measure of the toxicity or safety of a
drug and is defined as the ratio of the median
toxic dose to the median effective dose
– when the therapeutic index is high, it is reflected
by the wide range of dosages in which that drug is
prescribed
– When the therapeutic index is quite low, careful
monitoring of patients is required for whom the
drug is prescribed
 Pharmacokinetics
• Response to medication and sensitivity to side
effects are influenced by factors related to the
patient.
• This is why there is no one-size-fits-all approach to
pharmacological treatment.
• Patient-related variables include diagnosis, genetic
factors, lifestyle, overall medical status, concurrent
disorders, and history of drug response.
• A patient's attitude toward medication in general,
aversion to certain types of side effects, and
preference for a specific agent also need to be
considered.
• Dosing
– the clinically effective dose for treatment depends
on the characteristics of the drug and patient
factors, such as inherited sensitivity and ability to
metabolize a drug, concurrent medical disorders,
use of concurrent medications, and history of
exposure to previous medications.
• The potency of a drug refers to the relative
dose required to achieve certain effects, not
to its efficacy.
• Time of dosing is usually based on the plasma
half-life (t1/2) of a drug and its side effect
profile.
• Treatment Resistance
– some patients fail to respond to repeated trials of
medication
– strategies in these cases include the use of drug
combinations, high-dose therapy, and use of
unconventional drugs
• Tolerance
– marked by a need, over time, to use increased
doses of a drug for it to maintain a clinical effect
– also describes decreased sensitivity to adverse
effects of the drug, such as nausea
• Sensitization
– clinically manifested as the reverse of tolerance,
sensitization is said to occur when sensitivity to a
drug effect increases over time
– in these cases, the same dose typically produces
more pronounced effects as treatment progresses
• Withdrawal
– the development of physiological adaptation to a
drug
– technically, withdrawal should be considered a
side effect
• Combination of Drugs
– When two psychotropics with the same approved
indications are used concurrently, this is termed
combination therapy.
– Adding a drug with another indication is termed
augmentation.
 MOOD DISORDERS
• Depression
• Bipolar Disorders
– Mixed episode
– Mania
– Rapid cycling
• Hypomania
• Cyclothymia
• Dysthymia
• Others: SAD, premenstrual dysphoric disorder
 Five R‘s of Antidepressant Treatment
• Three terms beginning with the letter "R" are
used to describe the improvement of a depressed
patient after treatment with an antidepressant
• Response generally means that a depressed
patient has experienced at least a 50% reduction
in symptoms as assessed on a standard
psychiatric rating scale
• Remission is the term used when essentially all
symptoms go away, not just 50% of them
• If this lasts for 6 to 12 months, remission is then
considered to be Recovery
• Two terms beginning with the letter "R" are
used to describe worsening in a patient with
depression.
• If a patient worsens before there is a complete
remission or before the remission has turned
into a recovery, it is called a Relapse.
• However, if a patient worsens a few months
after complete recovery, it is called a
Recurrence.
The good news in the treatment of depression
• Half of depressed patients may recover within
6 months of an index episode of depression,
and three-fourths may recover within 2 years.

• Up to 90% of depressed patients may respond

to one or a combination of therapeutic
interventions if multiple therapies are tried.

• Antidepressants reduce relapse rates.

 The bad news in the treatment of depression
• "Pooping out" is common: the percentage of
patients who remain well during the 18-month
period following successful treatment for depression
is disappointingly low, only 70 to 80%.
• Many patients are "treatment-refractory": the
percentage of patients who are nonresponders and
who have a very poor outcome during long-term
follow-up evaluation after a diagnosis of depression
is disappointingly high, up to 20%.
• Up to half of patients may fail to attain remission,
including both those with "apathetic” responses and
those with "anxious" responses.
 ANTIDEPRESSANTS

A. Classical Antidepressants
1. MAOIs : Monoamine Oxidase Inhibitors
2. TCAs : Tricyclic Antidepressants

• MAOIs:
 1st antidepressants
 Side effects: can cause hypertensive crisis
restricts tyramine-containing foods
 drugs: Moclobemide (Aurorix)
Deprenyl (Selegiline)
• Tricyclic Antidepressants
drugs: Clomipramine (Anafranil)
Imipramine (Tofranil)
Maprotiline (Ludiomil)
Trimipramine (Surmontil)
May have cardiac side effects

• Selective Serotonin Reuptake Inhibitors

(SSRIs)
> Lack the danger in overdose that the tricyclics all
share
• Drugs:
Fluoxetine ( Prozac, Prodin, Motivest, Adepssir)
Sertraline ( Zoloft, Exulten, Zolodin, Zotral)
Paroxetine (Seroxat, Panex)
Fluvoxamine (Luvox, Fluvox)
Citalopram (Lupram, Feliz)
Escitalopram (Lexapro, Jovia, Zescita)
• Side effects : nausea and vomiting
paradoxical anxiety
sexual dysfunction, decreased
libido
• Selective Noradrenergic Reuptake Inhibitors
(NRIs)
More on the cognitive and affective symptoms of
depression
Drugs: Reboxetine
Duloxetine (Cymbalta)
> Side effects: dry mouth, constipation and urinary
retention
 Newer Antidepressants

• Serotonin and Noradrenergic Reuptake

Inhibitors (SNRIs)
Drugs: Venlafaxine (Effexor, Venlift)
Mirtazapine (Remeron, Mirazep)
Sibutramine – for obesity
 Mood Stabilizers
• Lithium
Very narrow therapeutic window
Side effects: nausea, vomiting
weight gain, tremors
thyroid and kidney problems
• Anticonvulsants
Drugs: Valproic Acid/Divalproate Na (Epival,
Depakote)
Carbamazepine (Tegretol)
Lamotrigine (Lamitor)
Gabapentin (Neurontin)
Topiramate (Topamax)

• Others: Benzodiazepines
Antipsychotics
• Electroconvulsive Therapy (ECT)
 Anxiolytics and Sedative-Hypnotics

• Benzodiazepines
Alprazolam (Xanor)
Clonazepam (Rivotril)
Diazepam ( Valium)
Lorazepam (Ativan)
Midazolam (Dalmane, Dormicum)

- Addictive and should be tapered slowly to avoid

withdrawal symptoms
• Adjunctive Treatments
Antihistamines – Diphenhydramine, Hydroxyzine
Beta-adrenergic blockers – Metoprolol
Alpha2 agonist- Clonidine

• Non-Benzodiazepine Short-Acting Hypnotics

Zolpidem (Stilnox)
Zaleplon
Zopiclone
• Sedating Antidepressants
Mirtazapine (Remeron)
 TCAs

• Natural products
Melatonin

• Older sedative-hypnotic
> Chloral hydrate
 Antipsychotic Agents
• neuroleptics
• typical or conventional
• Atypical or serotonin-dopamine antagonist or
dopamine-receptor antagonist
• Typical antipsychotics:
Chlorpromazine (Thorazine, Laractyl, Zycloran,
Proma, Psynor)
Haloperidol (Haldol, Seranace, Seredol)
Thioridazine (Melleril)
Trifluoperazine (Stelazine)
Depot preparation: Haloperidol decanoate
Fluphenazine decanoate
Fluphentixol decanoate
• Acts more on the positive symptoms
• Side effects: acute dystonia
tardive dyskinesia
NMS (neuroleptic malignant
syndrome)
galactorrhea
amenorrhea
cognitive blunting and social
withdrawal
dry mouth, blurred vision,
constipation
hypotension
• Atypical Antipsychotic : Serotonin-Dopamine
Antagonist
> Low EPS and efficacy for negative symptoms
Drugs: Clozapine (leponex, Ziproc, Syclop)
Risperidone (Risperdal, Zysda, Risdin)
Olanzapine (Zyprexa, Olanzapro)
Quetiapine (Seroquel, Ketilept)
Ziprasidone (Zeldox)
Aripiprazole (Abilify)
Sertindole (Serdolect)
Side effects: weight gain, hypotension, seizure and
agranulocytosis
 Cognitive Enhancers
• ADHD
Methyphenidate (Concerta)
Atomoxetine (Stattera)

• Dementia
Tacrine
Rivastigmine
Galantamine
Donepezil
Memantine
Vitamins and hormones – ginkgo biloba, Vit B12,
thiamine and zinc