Psych Drugs

Benzodiazapines
Benzodiazepines are the most frequently used anxiolytic drugs that prevent anxiety without causing
much associated sedation. In addition, they are less likely to cause physical dependence than many of
the older sedatives/hypnotics that are used to relieve anxiety.

The benzodiazepines act in the limbic system and the RAS to make gamma-aminobutyric acid (GABA)
more effective, causing interference with neuron firing. GABA stabilizes the postsynaptic cell. This
leads to an anxiolytic effect at doses lower than those required to induce sedation and hypnosis. The
exact mechanism of action is not clearly understood.

The benzodiazepines are indicated for the treatment of the following conditions: anxiety disorders,
alcohol withdrawal, hyperexcitability and agitation, and preoperative relief of anxiety and tension to
aid in balanced anesthesia.

Clonazepam (Klonopin)
Onset: varies
Duration: weeks

Alprazolam (Xanax)
Onset: 30 minutes
Duration: 4-6 hours

Lorazepam (Ativan)
Onset: 1-30 minutes
Duration: 12-24 hours

Contraindications to benzodiazepines include allergy to any benzodiazepine; psychosis, which could

be exacerbated by sedation; and acute narrow-angle glaucoma, shock, coma, or acute alcoholic
intoxication, all of which could be exacer-bated by the depressant effects of these drugs. In addition,
these sedative/hypnotics are contraindicated in pregnancy because a predictable syndrome of cleft lip
or palate, inguinal hernia, cardiac defects, microcephaly, or pyloric stenosis occurs when they are
taken in the first trimester. Neonatal withdrawal syndrome may also result. Breast-feeding is also a
contraindication
because of potential adverse effects on the neonate (e.g., sedation).Caution should be used in elderly
or debilitated patients
because of the possibility of unpredictable reactions and in cases of renal or hepatic dysfunction,
which may alter the metabolism and excretion of these drugs, resulting in direct toxicity. Dosage
adjustments usually are needed for such patients.

The adverse effects of benzodiazepines are associated with the impact of these drugs on the central
and peripheral nervous systems. Nervous system effects include sedation, drowsiness, depression,
lethargy, blurred vision, headaches, apathy, light-headedness, and confusion. In addition, mild
paradoxical excitatory reactions may occur during the first 2 weeks oftherapy.Several other kinds of
adverse effects may occur. GI conditions such as dry mouth, constipation, nausea, vomiting, and
elevated liver enzymes may result. Cardiovascular problems may include hypotension, hypertension,
arrhythmias, palpitations, and respiratory difficulties. Hematological conditions such as blood
dyscrasias and anemia are possible. Genitourinary (GU) effects include urinary retention and
hesitancy, loss of libido, and changes in sexual functioning. Because phlebitis, local reactions, and
thrombosis may occur at local injection sites, such sites should be monitored. Abrupt cessation of
these drugs may lead to a withdrawal syndrome characterized by nausea, headache, vertigo, malaise,
and nightmares

The risk of CNS depression increases if benzodiazepines are taken with alcohol or other CNS
depressants, so such combinations should be avoided. In addition, the effects of benzodiazepines
increase if they are taken with cimetidine, oral contraceptives, or disulfiram. If any of these drugs are
used with benzodiazepines, patients should be monitored and the appropriate dosage adjustments
made.
Flumazenil (Romazicon), a benzodiazepine antidote, acts by inhibiting the effects of the
benzodiazepines at the gamma-aminobutyric acid (GABA) receptors. It is used for three purposes: to
treat benzodiazepine overdose, to reverse the sedation caused by benzodiazepines that are used as
adjuncts for general anesthesia, and to reverse sedation produced for diagnostic tests or other
medical procedures.Flumazenil, which is available for IV use only, is injected into the tubing of a
running IV. The drug has a rapid onset of action that peaks 5 to 10 minutes after administration. It is
metabolized in the liver. Because this drug has a half-life of about 1 hour, it may be necessary to
repeat injections of flumazenil if a long-acting benzodiazepine was used. Patients who receive
flumazenil should be monitored continually, and life-support equipment should be readily available. If
the patient has been taking a benzodiazepine for a long period, administration of flumazenil may
precipitate a rapid withdrawal syndrome that necessitates supportive measures. Headache, dizziness,
vertigo, nausea, and vomiting may be associated with use of flumazenil

Selective Serotonin Reuptake Inhibitors (SSRI)

Selective serotonin reuptake inhibitors (SSRIs), the newest group of antidepressant drugs, specifically
block the reuptake of 5HT, with little to no known effect on NE. Because SSRIs do not have the many
adverse effects associated with TCAs and MAOIs, they are a better choice for many patients.

With the SSRIs, a period of up to 4 weeks is necessary for realization of the full therapeutic effect.
Patients may respond well to one SSRI and yet show little or no response to another one. The choice
of drug depends on the indications and individual response.

SSRIs are indicated for the treatment of depression, OCDs, panic attacks, bulimia, PMDD,
posttraumatic stress disorders, social phobias, and social anxiety disorders.

The SSRIs are contraindicated in the presence of allergy to any of these drugs and during pregnancy
and lactation because of the potential for serious adverse effects on the neonate. Caution should be
used in patients with impaired renal or hepatic function that could alter the metabolism and excretion
of the drug, leading to toxic effects, or with diabetes, which could be exacerbated by the stimulating
effects of these drugs.

The adverse effects associated with SSRIs, which are related to the effects of increased 5HT levels,
include CNS effects such as headache, drowsiness, dizziness, insomnia, anxiety, tremor, agitation, and
seizures. GI effects such as nausea, vomiting, diarrhea, dry mouth, anorexia, constipation, and
changes in taste often occur, as do GU effects, including painful menstruation, cystitis, sexual
dysfunction, urgency, and impotence. Respiratory changes may include cough, dyspnea, upper
respiratory infections, and pharyngitis. Other reported effects are sweating, rash, fever, and puritis.

Because of the risk of serotonin syndrome if SSRIs are used with MAOIs, this combination should be
avoided, and at least2 to 4 weeks should be allowed between use of the two types of drugs if
switching from one to the other. In addition, the use of SSRIs with TCAs results in increased
therapeutic and toxic effects. If these combinations are used, patients should be monitored closely,
and appropriate dosage adjustments should be made.

Fluoxetine (Prozac)

Citalopram (Celexa)

Duloxetine (Cymbalta)
Tricyclic Antidepressants

The tricyclic antidepressants (TCAs), including the amines, secondary amines, and tetracyclics, all
reduce the reuptake of 5HT and NE into nerves. Because all TCAs are similarly effective, the choice of
TCA depends on individual response to the drug and tolerance of adverse effects. A patient who does
not respond to one TCA may respond to another drug from this class.

The TCAs inhibit pre synaptic reuptake of the neurotransmitters NE and 5HT, which leads to an
accumulation of these neurotransmitters in the synaptic cleft and increased stimulation of the
postsynaptic receptors. The exact mechanism of action in decreasing depression is not known but is
thought to be related to the accumulation of NE and 5HT in certain areas of the brain.

TCAs are indicated for the relief of symptoms of depression. The sedative effects of these drugs may
make them more effective in patients whose depression is characterized by anxiety and sleep
disturbances. They are effective for treating enuresis in children older than 6 years. Some of these
drugs are being investigated for the treatment of chronic, intractable pain. In addition, the TCAs are
anticholinergic

One contraindication to the use of TCAs is the presence of allergy to any of the drugs in this class.
Other contraindications include recent myocardial infarction because of the potential occurrence of
reinfarction or extension of the infarct with the cardiac effects of the drug;myelography within the
previous 24 hours or in the next 48 hours; and concurrent use of an MAOI
because of the potential for serious adverse effects or toxic reactions. In addition, pregnancy and
lactation are contraindications because of the potential for adverse effects in the fetus and neonate.
Caution should be used with TCAs in patients with pre-existing cardiovascular (CV) disorders because
of the cardiac stimulatory effects of the drug and with any condition that would be exacerbated by the
anticholinergic effects, such as angle-closure glaucoma, urinary retention, prostate hypertrophy, or GI
or genitourinary (GU) surgery. Care should also be taken with psychiatric patients, who may exhibit a
worsening of psychoses or paranoia, and with manic depressive patients, who may shift to a manic
stage. In addition, caution is necessary in patients with a history of seizures because the seizure
threshold may be decreased secondary to stimulation of the receptor sites and in elderly patients. The
presence of hepatic or renal disease, which could interfere with metabolism and excretion of these
drugs and lead to toxic levels, also necessitates caution.

The adverse effects of TCAs are associated with the effects of the drugs on the central nervous
system (CNS) and on the peripheral nervous system. Sedation, sleep disturbances, fatigue,
hallucinations, disorientation, visual disturbances, difficulty in concentrating, weakness, ataxia, and
tremors may occur. Use of TCAs may lead to GI anticholinergic effects, such as dry mouth,
constipation, nausea, vomiting, anorexia, in-creased salivation, cramps, and diarrhea. Resultant GU
effects may include urinary retention and hesitancy, loss of libido, and changes in sexual functioning.
CV effects such as orthostatic hypotension, hypertension, arrhythmias, myocardial infarction, angina,
palpitations, and stroke may also pose problems. Miscellaneous reported effects include alopecia,
weight gain or loss, flushing, chills, and nasal congestion. These adverse effects may be intolerable to
some patients, who then stop taking the particular TCA. Abrupt cessation of all TCAs causes a
withdrawal syndrome characterized by nausea, headache, vertigo, malaise, and nightmares.

If TCAs are given with cimetidine, fluoxetine, or ranitidine, an increase in TCA levels results, with an
increase in both therapeutic and adverse effects, especially anticholinergic conditions. Patients should
be monitored closely, and appropriate dosage reductions should be made. Other drug combinations
may also pose problems. The combination of TCAs and oral anticoagulants leads to higher serum
levels of the anticoagulants and increased risk of bleeding. Blood tests should be done frequently, and
appropriate dosage adjustments in the oral anticoagulant should be made. If TCAs are combined with
sympathomimetics or clonidine, the risk of arrhythmias and hypertension is increased. This
combination should be avoided, especially in patients with underlying cardiovascular disease. The
combination of TCAs with MAOIs leads to a risk of severe hyperpyretic crisis with severe convulsions,
hypertensive episodes, and death. This combination should be avoided. Although TCAs and MAOIs
have been used together in selected patients who do not respond to a single agent, the risk of severe
adverse effects is very high

Amitriptyline (Elavil)

Antimanics

Eskalith or Lithobid (Lithium Carbonate)

Mania, the opposite of depression, occurs in individuals with bipolar disorder, who experience a period
of depression followed by a period of mania. The cause of mania is not under-stood, but it is thought
to be an overstimulation of certain neurons in the brain. The mainstay for treatment of manias lithium.
Lithium salts (Lithane, Lithotabs) are taken orally for the management of manic episodes and
prevention of future episodes. These very toxic drugs can cause severe CNS, renal, and pulmonary
problems that may lead to death. Despite the potential for serious adverse effects, lithium is used
with caution because it is consistently effective in the treatment of mania. The therapeutically
effective serum level is 0.6 to1.2 mEq/L.

Lithium functions in several ways. It alters sodium transport in nerve and muscle cells; inhibits the
release of norepinephrine and dopamine, but not serotonin, from stimulated neurons; increases the
intra-neuronal stores of norepinephrineand dopamine slightly; and decreases intra-neuronal content of
second messengers. This last mode of action may allow it to selectively modulate the responsiveness
of hyperactive neurons that might contribute to the manic state. Although the biochemical actions of
lithium are known, the exact mechanism of action in decreasing the manifestations of mania are not
understood.

Lithium is indicated for the treatment of manic episodes of manic-depressive or bipolar illness and for
maintenance therapy to prevent or diminish the frequency and intensity of future manic episodes.
This agent is currently being investigated for the improvement of neutrophil counts in patients with
cancer chemotherapy-induced neutropenia and as prophylaxis of cluster headaches and migraine
headaches.

Lithium is contraindicated in the presence of hypersensitivity to lithium. In addition, it is

contraindicated in the following conditions: significant renal or cardiac disease that could be
exacerbated by the toxic effects of the drug; a history of leukemia; metabolic disorders, including
sodium depletion; dehydration; and diuretic use because lithium depletes sodium reabsorption, and
severe hyponatremia may occur. (Hyponatremia leads to lithium retention and toxicity.)Pregnancy
and lactation are also contraindications because of the potential for adverse effects on the fetus or
neonate. Caution should be used in any condition that could alter sodium levels, such as protracted
diarrhea or excessive sweating; with suicidal or impulsive patients; and in patients who have infection
with fever, which could be exacerbated by the toxic effects of the drug.

The adverse effects associated with lithium are directly related to serum levels of the drug.

Serum levels of less than 1.5 mEq/L:

CNS problems, including lethargy, slurred speech, muscle weakness, and fine tremor; polyuria, which
relates to renal toxicity; and beginning of gastric toxicity, with nausea, vomiting, and diarrhea
Serum levels of 1.5 to 2 mEq/L:
Intensification of all of the above reactions, with ECG changes•

Serum levels of 2 to 2.5 mEq/L:

Possible progression of CNS effects to ataxia, clonic movements, hyperreflexia,and seizures; possible
CV effects such as severe ECGchanges and hypotension; large output of dilute urine secondary to
renal toxicity; fatalities secondary to pulmonary toxicity

Serum levels greater than 2.5 mEq/L:

Complex multi-organ toxicity, with a significant risk of death

Some drug–drug combinations should be avoided. A lithium–haloperidol combination may result in an

encephalopathic syndrome, consisting of weakness, lethargy, con-fusion, tremors, extrapyramidal
symptoms, leukocytosis, and irreversible brain damage. If lithium is given with carbamazepine
increased CNS toxicity may occur, and a lithium–iodide salt combination results in an increased risk of
hypothyroidism. Patients who receive either of these combinations should be monitored carefully. In
addition, a thiazide diuretic–lithium combination increases the risk of lithium toxicity because of the
loss of sodium and increased retention of lithium. If this combination is used, the dosage of lithium
should be decreased and the patient should be monitored closely. In the following instances, the
serum lithium level should be monitored closely and appropriate dosage adjustments made. With the
combination of lithium and some urine-alkalinizing drugs, including antacids and trometh-amine, there
is a possibility of decreased effectiveness of lithium. If lithium is combined with indomethacin or with
some nonsteroidal anti-inflammatory drugs, higher plasma levels of lithium occur.

Divalproex (Depakote)

Divalproex is commonly prescribed for migraine prevention and the treatment of epilepsy and manic
episodes associated with bipolar disorder. The drug works by affecting sodium channels in the brain
and increasing the amount of a certain brain chemical (GABA). Various divalproex products are
available, including delayed-release tablets and sprinkle capsules. Possible side effects include
headaches, shakiness, and drowsiness.

Cholinesterase Inhibitors

All of the indirect-acting cholinergic agonists work by blocking acetylcholinesterase at the synaptic
cleft. This blocking allows the accumulation of ACh released from the nerve endings and leads to
increased and prolonged stimulation of ACh receptor sites at all of the postsynaptic cholinergic sites.
These drugs can work to relieve the signs and symptoms of myasthenia gravis and increase muscle
strength by accumulating ACh in the synaptic cleft at neuromuscular junctions

These drugs are contraindicated in the presence of allergy to any of these drugs; with bradycardia or
intestinal or urinary tract obstruction, which could be exacerbated by the stimulation of cholinergic
receptors;
in pregnancy because the uterus could be stimulated and labor induced; and during lactation because
of the potential effects on the baby. Caution should be used with any condition that could be
exacerbated by cholinergic stimulation. Although the effects of these drugs are generally more
localized to the cortex and the neuromuscular junction, the possibility of parasympathetic effects
should be considered carefully in patients with asthma, coronary disease, peptic ulcer, arrhythmias,
epilepsy, or Parkinsonism.

The adverse effects associated with these drugs are related to the stimulation of the parasympathetic
nervous system. GI
effects can include nausea, vomiting, cramps, diarrhea, in-creased salivation, and involuntary
defecation related to the increase in GI secretions and activity caused by parasympathetic nervous
system stimulation. Cardiovascular effects can include bradycardia, heart block, hypotension, and
even cardiac arrest, related to the cardiac-suppressing effects of the parasympathetic nervous
system. Urinary tract effects can include a sense of urgency related to stimulation of the bladder
muscles and sphincter relaxation. Miosis and blurred vision, headaches, dizziness, and drowsiness can
occur related to CNS cholinergic effects. Other effects may include flushing and increased sweating
secondary to stimulation of the cholinergic receptors in the sympathetic nervous system.

There may be an increased risk of GI bleeding if these drugs are used with nonsteroidal anti-
inflammatory drugs (NSAIDs)
because of the combination of increased GI secretions and the GI mucosal erosion associated with the
use of NSAIDs. If this combination is used, the patient should be monitored closely for any sign of GI
bleeding. The effect of anticholinesterasedrugs is decreased if they are taken in combination with any
cholinergic drugs because these work in opposition to each other. Theophylline levels can be
increased up to twofold if combined with tacrine; if that combination is used, the dosage of
theophylline should be reduced accordingly and the patient monitored closely

Galantamine (Reminyl)
Tacrine ( Cognex)
Donezepril ( Aricept)

Monoamine Oxidase Inhibitors (MAO)

The monoamine oxidase (MAO) inhibitors irreversibly inhibit MAO, an enzyme found in nerves and
other tissues (including the liver), that breaks down the biogenic amines NE, dopamine, and 5HT. This
allows these amines to accumulate in the synaptic cleft and in neuronal storage vesicles, causing
increased stimulation of the postsynaptic receptors and, it is thought, relief of depression. The MAOIs
are generally indicated for treatment of the signs and symptoms of depression in patients who cannot
tolerate or do not respond to other, safer antidepressants.

Contraindications to the use of MAOIs include allergy to any of these antidepressants;

pheochromocytoma because the sudden increases in NE levels could result in severe hyper-tension
and CV emergencies; CV disease, including hyper-tension, coronary artery disease, angina, and
congestive heart failure, which could be exacerbated by increased NE levels;
And known abnormal CNS vessels or defects because the potential increase in blood pressure and
vasoconstriction associated with higher NE levels could precipitate a stroke. A history of headaches
may also be a contraindication. Other contraindications include renal or hepatic impairment, which
could alter the metabolism and excretion of these drugs and lead to toxic levels, and myelography
within the past 24 hours or in the next 48 hours
because of the risk of severe reaction to the dye used in myelography.In addition, caution should be
used with psychiatric patients, who could be over stimulated or shift to a manic phase as a result of
the stimulation associated with MAOIs, and in patients with seizure disorders or hyperthyroidism, both
of which could be exacerbated by the stimulation of these drugs. Care should also be taken with
patients who are soon to undergo elective surgery because of the potential for unexpected effects
with NE accumulation during the stress reaction, and with female patients who are pregnant or breast-
feeding because of potential adverse effects on the fetus and neonate.

The MAOIs are associated with more adverse effects, more of which are fatal, than most other
antidepressants. The effects relate to the accumulation of NE in the synaptic cleft. Dizziness,
excitement, nervousness, mania, hyperreflexia, tremors, confusion, insomnia, agitation, and blurred
vision may occur.MAOIs can cause liver toxicity. Other GI effects can include nausea, vomiting,
diarrhea or constipation, anorexia, weight gain, dry mouth, and abdominal pain. Urinary retention,
dysuria, incontinence, and changes in sexual function may also occur. Cardiovascular effects can
include orthostatic hypotension, arrhythmias, palpitations, angina, and the potentially fatal
hypertensive crisis. This last condition is characterized by occipital headache, palpitations, neck
stiffness, nausea, vomiting, sweating, dilated pupils, photophobia, tachycardia, and chest pain. It may
progress to intracranial bleeding and fatal stroke.

Drug interactions of MAOIs with other antidepressants include hypertensive crisis, coma, and severe
convulsions with TCAs, and a potentially life-threatening serotonin syndrome withSSRIs. A period of 6
weeks should elapse after stopping an SSRI before beginning therapy with an MAOI.If MAOIs are given
with other sympathomimetic drugs (e.g., methyldopa, guanethidine), sympathomimetic effects
increase. Combinations with insulin or oral antidiabeticagents result in additive hypoglycemic effects.
Patients who receive these combinations must be monitored closely, and appropriate dosage
adjustments should be made.

Tyramine and other pressor amines that are found in food, which are normally broken down by MAO
enzymes in the GI tract, may be absorbed in high concentrations in the presence of MAOIs, resulting
in increased blood pressure. The hypertensive crisis is often associated with eating foods that contain
tyramine. In addition, tyramine causes the release of stored NE from nerve terminals, which further
contributes to high blood pressure.

Phenelzine (Nardil)

Other Antidepressants

Some other effective antidepressants do not fit into any of the three groups that have been discussed
in this chapter. These drugs have varying effects on NE, 5HT, and dopamine. Although it is not known
how their actions are related to clinical efficacy, these agents may be most effective in treating
depression in patients who do not respond to other anti-depressants

Bupropion (Wellbutrin)

Venlafaxine ( Effexor)

Mirtazapine (Remeron)

Anxiolytics

Other drugs are used to treat anxiety or to produce hypnosis that do not fall into either the
benzodiazepine or the barbiturate group.

Buspirone (BuSpar), a newer antianxiety agent, has non sedative, anticonvulsant, or muscle-relaxant
properties and its mechanism of action are unknown. However, it reduces the signs and symptoms of
anxiety without many of the CNS effects and severe adverse effects associated with other anxiolytic
drugs. It is rapidly absorbed from the GI tract, metabolized in the liver, and excreted in urine. Caution
should be used in patients with hepatic or renal impairment and in elderly patients.

Buspirone (BuSpar)
N-Methyl-D-Aspartate (NMDA) Receptor Antagonists

Memantine regulates glutamate, a chemical involved in information processing, storage and retrieval.
It is thought that glutamate – the brain’s primary excitatory neurotransmitter – plays a significant role
in the neuronal cell death that is common to all neurodegenerative diseases. As neurons are damaged
– in Alzheimer’s, for example, by the deposition of amyloid – that damage leads to an excess release
of glutamate, which neuroscientists refer to as ‘overexcitation’. By blocking the action of glutamate at
NMDA receptors, Memantine directly short-circuits the overexcitation.

Memantine use should be carefully monitored by your doctor if you have a history of seizures or have
recently had a heart attack, kidney disease or untreated hypertension. Memantine may interact with
some other drugs such as Dextromethorphane, Cimetidine, procainamide, hydrochlorothiazide,
anticholinergics, anticonvulsives, barbiturates or dopaminergic antagonists like L-dopa or Parlodel
(bromocriptine). Make sure the doctor knows what else the person with dementia is taking.

SIDE EFFECTS: Tiredness, body aches, dizziness, constipation, and headache may occur. If any of
these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the
benefit to you is greater than the risk of side effects. Many people using this medication do not have
serious side effects.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it
occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the
face/tongue/throat), severe dizziness, trouble breathing.

Memantine (Namenda)