PHARMACOTHERAPY IN PSCHIATRY
DEPRESSION
SCHIZOPHRENIA
BIPOLAR DISORDERS
SCHIZOPHRENIA ETHIOLOGY Exact etiology unknown Genetic predisposition Intrauterine, birth or postnatal complications Viral CNS infections Environmental stressors (biochemical or social) No evidence of association with poor parenting
POSITIVE SYMPTOMS
NEGATIVE SYMPTOMS
Hallucination
Social withdrawal
Delusions
Emotional withdrawal
Disordered thinking
Lack of motivation
Disorder speech
Poverty of speech
Combativeness
Blunted affect
Agitation
Poor insight
Paranoia
Poor judgement Poor self-care
ANTIPSYCHOTICS
Typical/conventional antipsychotics
Atypical antipsychotics
TYPICAL/ CONVENTIONAL ANTIPSYCHOTICS
Chlorphomazine (Largactic)
Sulpiride (Dogmatil)
Haloperidol (Serenace, Haldol)
Thioridazine (Melleril)
Flupenthixol (Fluanxol)
Trifluoperazine (Stelazine)
Pericyazine (Neulactil)
Thiothixene (Navane)
Pimozide (Orap, Orap Forte)
also known as
“dopamine receptor antagonist”
-pharmacologic activity at blocking central dopamine receptors (esp. D2 receptors)
“neuroleptics” -due to tendency to cause neurologic adverse effects
“major tranquilizers”
-inappropriate as these agents (esp. high potency) can improve psychosis without sedating or making patients tranquil
Mechanism of action
Blocks receptors for dopamine, acetylcholine, histamine and noreepinephrine
Current theory suggests Dopamine2 (D2) receptors suppresses psychotic symptoms
All typical antipsychotics block D2 receptors
Close correlation between clinical potency and potency as D2 receptor antagonists
Adverse effects
Extrapyramidal symptoms (EPS)
Early reactions- can be managed with ddrugs Acute dystonia Parkinsonism Akathsiia
Late reaction - drug treatment unsatisfactory
Tardive dyskinesia
Early reactions occur less frequently with low potency drugs
Risk od TD is equal with all agents
ATYPICAL ANTIPSYCHOTICS
Refers to new agents
Also known as
“Serotonin-dopamine antagonists”
Postsynaptic effects at 5-HT2A and D2 receptors
Amisulpiride (Solian)
Quetiapine (Seroquel)
Ziprasidone (Zeldox)
Clozapine (Clozaril)
Risperidone (Risperdal)
Aripiprazole (Abilify)
Olanzapine (Zyprexa)
Clozapine
Contraindication
History of clozapine-induced agranulocytosis
Bone marrow suppression
On myelosuppressive drugs
Caution
Seizure disorders
Diabetes
NON-ANTIPSYCHOTIC AGENTS Benzodiazepines
Useful in some studies for anxiety, agitation, global impairment and psychosis
Schizophrenic patients are prone to BZD abuse
Limit use shorts trials (2-4 weeks) for management of severe agitation and anxiety
Lithium
Limited role in schhizophrenia monotherapy
Improve psychosis, depression, excitement and irritability when used with antipsychotic in some studies.
DEPRESSION
Depressed mood and/or decrease in interest in things that used to give pleasure
Sadness severe enough or persistent enough to interfere with funtion
DSM-IV
Major depressive disorder / major depression
Dysthymia
depressive for most of the day, more days than not
Depressive disorder not otherwise specified
Depressive disorder due to a general physical condition
Substance-induced depressive disorder
Epidemiology
Life prevalence 3-17%
Onset in late 20s
Highest in
25-44 years
Elderly in community
Female vs Male = 2:1
Female 10-20% lifetime risk
Male 5-12% lifetime risk
Signs and symptoms
Depressed mood
Concentration loss
Sleep (insomia or hypersomnia)
Appetite (loss or gain)
Loss of interest (including libido)
Guilt
Psychomotor (agitation or retardation)
Energy loss
Suicide (ideation)
Pathophysiology
Exact course unknown
Change in receptor-neurotransmitter relationship in limbic system
Serotonin, norepinephrine, somtimes dopamine
Increased pump uptake of neurotransmitters
Reabsorption into neuron
Destroyed by monoamine oxidase in mitochondria
Lack of neurotransmitters
Antidepressants
Tricyclic and related antidepressants (TCA) e.g. amitriptyline, imipramine, doxepin, mianserin, trazodone
Monoamine-oxidase inhibitors (MAOI) e.g. moclobemide, phenelzine, isocarboxazid, tranylcypromine
Selective serotonin reuptake inhibitors (SSRI) e.g. fluoxetine, paraxetine, sertraline, citalopram
Other antidepressants e. mirtazapine, venlafaxine, duloxetine, flupentixol
Tricyclic and related antidepressants (TCA)
Amitriptyline (Saroten)
Mianserin (Tolvon)
Clomipramine (Anafranil)
Nortriptyline (Nortrilen)
Dothiepin (a.k.a. Dosulepin, Prothiaden)
Trazodone (Trittico)
Trimipramine (Surmontil)
Imipramine (Tofranil)
Mechanism of action
Blocks neuronal uptake or norepinephrine and serotonin
Initial response develops in 1-3 weeks
Maximal response develops in 1-2 months
Older tricyclic
Marked anticholinergic adversse effects
Risk of carditoxicity
Tricyclic-related drugs (e.g. trazodone)
Fewer anticholinergic adverse effects
Sedation, dizziness, priapism (persistent penile erection accompanied by pain and tenderness)
Properties
Inexpensive, generic
Some with off-label use, e.g.
Neuropathy with amitriptyline
Refractory skin diseases with doxepin
Very dangerous in overdose
Life threatening
Lethal dose only 8 times average daily dose
Acutely depressed patients should not be given more than 1-week TCA supply at one time
Monoamine-oxidase inhibitors (MAOI) Properties
Useful in atypical depression (somnolence and weight gain), refractory disorder and certain types of anxiety disorders
Less prescribed than tricyclics, SSRIs and other antidepressants
Danger of dietary and drug interactions
Adverse effects
Hypertensive crisis Severe occipital headache, photophobia, palpitation, sharply increased in BP due to addictive effect between MAOI and adrenergic stimulants Tyramine-rich food e.g. cheese, wine, smoked/aged picked meat or fish, alcohol Amphetamine Pseudoephedrine