Psychiatric or
Psychotropic
or Psychotherapeutic
Medications
Antianxiety drugs
Antidepressants
Antipsychotics
Antidepressants
Symptoms of Major
Depression
l sadness, feel helpless,
hopeless, worthless, inappropriate guilt
l no energy, apathetic, nothing
matters
l can’t make decisions,
complete tasks
l lose appetite for food &
sex, disordered sleep, may move & talk slowly
l suicidal thoughts or actions
Brain Changes in
Depression
l This family of transmitters
is known as the monoamines.
Monoamine Theory of
Mood
l Normal mood depends on
adequate levels of monoamine activity in brain.
l Levels too low à
depression
l Levels too highà
euphoria, mania
l Attention focused on NE early
in the drug treatment of depression; now its clear that serotonin (5HT) is also
critical, maybe DA too.
l Probably different
depressions associated with different imbalances.
Categories of
Antidepressants
l Tricyclic antidepressants
(TCAs)
l Monoamine oxidase inhibitors
(MAOIs)
l Selective serotonin reuptake
inhibitors (SSRIs)
l Miscellaneous newer drugs
with various actions
Tricyclic
Antidepressants (TCAs)
l Best known:
»
*imipramine
(Tofranil)
»
*amitriptyline
(Elavil, Endep)
»
desipramine
(Norpramin)
»
Nortriptyline
(Pamelor, Aventyl)
l Consistently, significantly
more effective than placebo in providing relief for even the most severe
depression & sustained prevention of depressive episodes. Not as effective
for psychotic or atypical forms.
l Usually taken once a day at
bedtime
Action of
Tricyclics – block reuptake of monoamines
Tricyclic Problems
l Delayed effectiveness (3-5
weeks); therapeutic window for effectiveness
l Also block ACh and histamine,
causing annoying side effects before benefits are felt:
»
Anticholinergic:
Dry mouth, blurred vision, constipation, urinary hesitance,
tachycardia,possible memory problems
»
Antihistamine:
sedation, possible weight gain
l Have a low safety margin
& are lethal in overdose (cause cardiac arrhythmia & heart failure) and
interact with a wide variety of drugs. #1 cause of prescription drug overdose
death in US.
Other Uses for
Tricyclics
l treatment of chronic pain
l treatment of enuresis
(bed-wetting)
l some cases of ADHD and OCD
l panic disorder/agoraphobia,
and probably other anxiety disorders
MAO Inhibitors
(MAOIs)
l phenelzine (Nardil),
tranylcypromine (Parnate), isocarboxazid (Marplan)
l Inhibit action of MAO, an
enzyme which breaks down 5HT, DA and NE, allowing more transmitter release.
Action of MAOI’s –
inhibit an enzyme that breaks down monoamines
MAOI Problems
l Foods with high levels of
tyramine must be avoided (strict attention to diet)
l Drugs with sympathomimetic
actions must be avoided
l Neglecting restrictions can
result in life-threatening hypertensive crisis (severe headache, skyrocketing
blood pressure, heart palpitations); must continue restrictions 2 weeks after
stopping drug as well
l Clinical improvement delayed
1-4 weeks
Uses for MAO
Inhibitors
l Because of potential side
effects, MAOIs are not usually a first line treatment
l But may be beneficial for
atypical depression, panic disorder, bipolar depression, depression in the
elderly
l More selective and reversible
MAO inhibitors that don’t require dietary restrictions are being used in Europe
Selective Serotonin
Reuptake Inhibitors (SSRIs)
l fluoxetine* (Prozac, Serafem)*, paroxetine (Paxil), sertraline
(Zoloft), fluvoxamine (Luvox), citalopram (Celexa; Lexipro)
l same effectiveness but more
acceptable side effects and fewer risks; patients more willing to take SSRIs
l side effects more like
stimulant drugs (feel anxious, hyper, restless, suffer insomnia, stomach upset,
diarrhea)
Action of SSRIs –
block reuptake of 5HT only
SSRI Problems
l Not cheap!
l Significant proportion
(~30-60%?) will have sexual side effects (loss of desire, impotence, difficulty
achieving orgasm)
l Risk of Serotonin syndrome (dangerous over-stimulation
with confusion, agitation and overactivation of body) with high doses or if
combined with other 5HT-related drugs
l Risk of Serotonin Withdrawal
Syndrome
when you stop using SSRIs (dizziness, nausea, flu-like illness, sensory
abnormalities, sleep disturbances)
Other Uses for
SSRIs
l Used for obsessive-compulsive
disorder
l Used for social phobias,
panic disorder, PTSD, generalized anxiety disorder
l Treatment of some eating
disorders & addictions and some chronic headaches
l Treatment of dysthymia
(milder depression); pre-menstrual dysphoria, postpartum depression, bipolar
depression
l Some use for borderline and
schizotypal personality disorders
Return of “Dual
Action” Drugs
» Efflexor (venlafaxine)* –
similar to TCAs without the side effects and risks
» None of the sexual effects of
SSRIs
» Has been effective for many
patients who have failed to improve using the other drugs
»
May
be somewhat more effective and faster than the other drugs
Drugs Not Fitting
Above Categories
l New mechanisms of action
l None are “wonder drugs” but
each might be appropriate for particular patients
l Fewer effects on sexual
functioning
»
*Wellbutrin
(buproprion) (some
seizure risk)
»
Desyrel
(trazodone) (faster,less
anticholinergic)
»
Serzone
(nefazadone) (no
sex effects, is sedative)
»
Remeron
(mirtazapine) (no
sex effects, is sedative)
What About Placebo
Effects?
l Significant placebo effect
(~40% of placebo group improve during study)
l But nearly 70% improve on
drug
l ~57% relapse on placebo; 26%
relapse on drug
The Monoamine
Theory
l Old theory: mood depends on
adequate levels of monoamine activity
l Availability is not enough -
drugs all increase availability immediately but don’t become clinically
effective for a few weeks
l Hypothesis: improved mood
depends on a slower adaptation of CNS to increased availability
(“down-regulation of receptors”)
St. Johns-Wort
(Hypericum perforatum)
l ~300 mg of .3% hypericin
extract is effective in treating mild /moderate depression
l takes several weeks to work
l Combination of mild MAOI and
SSRI actions
l side effects: restlessness,
stomach upset, photosensitivity
l don’t use WITH other
antidepressants
Bipolar Disorder
a.k.a.
manic-depressive disorder
l Depression alternating with
mania/hypomania, e.g.:
» increased energy, excitement,
activity & speech
» decreased need for sleep; may
be restless, irritable
» impulsive; unrealistic
confidence, grandiose plans
» may show increased social,
sexual, work activities
» may be delusional
Mood-Stabilizing
Drugs
Bipolar Disorder
l Drug of choice has been
lithium carbonate (e.g. Eskalith)
l Seems to increase reuptake
and alter receptor and membrane sensitivity but the way that it moderates both
extremes of mood is really not understood
l Takes 7-10 days to act, 2-3
weeks for maximal effect
l About 50% get good control of
their disorder; not as effective for “mixed” cases. Also helps prevent future
attacks in ~50%
*Lithium
l Alkali metal like sodium or
potassium
l Side effects: thirst,
increased urination, gastric upset, tremor, skin problems, weight gain
l These decrease some with
tolerance as long as blood levels don’t creep up or body salt levels don’t fall
l Problem: up to 50%
non-compliance rate
l Need regular blood tests to
avoid excess lithium & toxicity and to check thyroid & kidney function
Lithium Toxicity
l Side effects become more
pronounced:
l Worse tremors &
incoordination
l Excess cognitive/behavioral
slowing, fatigue, slurred speech
l Rigidity, seizures & coma
possible
Alternatives for
Mania:
Anticonvulsants
& Antipsychotics
l *valproate/divalproex
(Depakote, Depakene)
»
May
work faster than lithium; good for “mixed” cases
l carbamazepine (Tegretol)
»
Not
quite as effective as lithium or valproate
l Several new anticonvulsants
being studied
l Antipsychotic medications
(haloperidol (Haldol), olanzapine (Zyprexa))
»
Have
been used for sedation of an acute manic episode and for longer term therapy
l Many individuals may require
a combination of lithium and anticonvulsant or addition of an antidepressant
Other Drugs in Use
l Other atypical antipsychotics Risperdol (risperidone),
Clozaril (clozapine) being investigated as a first-line therapy – looks
promising
l Antidepressants used (with
care) for depressive part of cycle – too much antidepressant can sometimes
trigger the manic phase
l Benzodiazepine tranquilizer(
clonazepam (Clonopin) for calming effects
l Omega-3 fatty acids being investigated