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Psychopharmacology: Medications for the Mind

4.00 Contact Hours:
A score of 80% correct answers on a test is required to successfully complete any course and attain a certificate of completion.
Authors:    David Tilton (RN, BSN) , Susan Tilton (BSB BSMT)

Purpose/Goals

Medications for the mind have a powerful effect. Important treatments center on altering the chemical balance of the brain. Often, in our fast-paced professional lives, it is difficult to remember the classifications and use of medications seen on an infrequent basis. It is important to routinely refresh our own memory, exercise cognitive processes, and review briefly the medications for the mind, psychopharmacology.

Objectives

On completion of this educational activity, participants will be able to;

  1. Identify two major categories of psychopharmacology agents
  2. Describe the effect desired from Mood Stabilizers
  3. Distinguish how the mechanisms of action vary between antidepressant groups
  4. Explain two uses of psychostimulant medications
  5. Explain two uses of psychostimulant medications

Introduction

Psychopharmacology is the study and use of medications that effect thought or behavior. People ingest vast quantities of prescription psychopharmaceuticals. The benefit of prescription psychoactive agents is the lessening in symptoms of mental disorders, either acute or chronic in nature. As a general medication category, psychopharmacology agents, especially antidepressants and antipsychotics, are among the most widely prescribed pharmaceuticals of our generation. Psychostimulants find use among our children. Sedatives and hypnotics aid adults in dealing with the day-to-day stress created by our frantic lifestyles.

Research gathered in 2006 revealed that one in ten adults and one in twenty children in the U. S. are taking prescription mental health medication. The prevalence of these helpful and therapeutic medications creates a need for awareness among health professionals concerning the basics related to psychoactive pharmacology, the medications for the mind (Wang, S., 2009).

In Your Head

Medications whose purpose is to alter the chemical balance in the brain and central nervous system (CNS) are widely used. The treatment of mental illness symptoms, mood disturbance, and even inability to focus attention all employ prescription substances that affect the mind. Medications designed to alter brain chemistry are as a general grouping referred to as psychopharmacology medications, although terms ranging from neuropsychopharmacology to just plain “psych meds” are used as general identifiers.

Psychopharmacology medications fall into loose categories based on the chemistry of how they work in our body or their primary effect on the central nervous system. Some medications used in psychiatric care have effect in more than one area. Common groupings are:

  • Antianxiety Agents
  • Antidepressants
  • Antipsychotics
  • Mood Stabilizers
  • Psychostimulants

Each of the medications that fall into these groupings possess the ability to influence or affect the chemistry within the brain. Special emphasis has been placed on the role that chemicals known as neurotransmitters play due to recent insights into the cellular structure of key brain cells and the critical function of these chemical messengers.

Neurotransmitters

Neurotransmitters such as dopamine and serotonin are manufactured in nerve cells known as neurons for the purpose of conveying messages from cell to cell across a tiny physical space between nerve cells known as the synaptic gap. The nerve cell structure sending the message, called the axon, exudes messenger chemicals, neurotransmitters, towards the receiving structure, a dendrite, on the next nerve cell of the message chain. The surface of the receiving dendrite is covered with specialized proteins that act as receptor sites for messenger chemicals. Receptor sites have special characteristics that respond to the unique shape of each specific neurotransmitter, much as the lock on your front door responds only to the unique shape of the key in your hand. Once a neurotransmitter is received into a corresponding receptor site the chemical messenger is either destroyed or reabsorbed and taken out of circulation.
neurotransmitters

Some neurotransmitters have multiple messages they can convey, depending on factors such as which area of the nervous system where they are released into.

Changes in neurotransmitter structure, alterations in the amount of neurotransmitter available to be received or in the number of available receptor sites for a particular neurotransmitter all effect the message being sent. Results of a change in neurotransmitter balance or availability may affect thoughts, emotions, behaviors, and mental processes.

The total number of distinct neurotransmitters used within the central nervous system is not known. Over a hundred information carrying molecules have already been discovered, each of which has an important, if often times mysterious, role to play. Only a few of these chemical couriers are currently amiable to pharmaceutical manipulation, generally by boosting or suppressing their functional availability. However, what can be accessed allows new treatment mechanisms and new tools to ease undesired symptoms found in the mental or emotional realm (Purves, D., et al., 2007).

Select Neurotransmitter Function
Acetylcholine
(ACh)
Acetylcholine was the first neurotransmitter recognized, in 1921, for the role it plays, and resulted in a Nobel Prize.
It stimulates muscles, aids in sensory function, facilitates REM sleep, attention, motivation, learning, and memory. Too much ACh can lead to muscle spasms, tremors, and movement disorders. Insufficient ACh leads to a state of torpor or paralysis.
Dopamine Dopamine is strongly associated with brain reward mechanisms, arousal, and general physical motivation. If a feeling of anticipation is present proceeding an action, activity or consuming a substance, dopamine is likely involved.
Too much dopamine has been associated with Schizophrenia, while too little accompanies Parkinson’s disease and social anxiety disorders.
Endorphins
(enkephalins)
Endorphins are a group of very similar neurochemicals. Every runner has heard of endorphins. They function similarly to opioid narcotics. Their presence reduces pain perception and effects pleasure, they tend to reduce stress, and enhance calm feelings.
GABA
(gamma aminobutyric acid)
GABA slows the excitation that leads to anxiety. Its presence has been linked to sleep and eating disorders. Too little GABA is associated with anxiety disorders and even epilepsy.
Glutamate Glutamate is the most common neurotransmitter in the CNS, and is very important to memory function as well as how pain is perceived. Excess glutamate is associated with the destruction of brain cells, such as in ALS/ Lou Gehrig’s disease.
Norepinephrine
(noradrenalin)
Norepinephrine also won its discoverer a Nobel Prize.
This is the “high alert” transmitter, increasing heart rate and blood pressure to deal with stress or danger. It prompts both physical and mental arousal, and can elevate the mood. It is also important for forming lasting memories.
Serotonin The link between serotonin and mood has been widely discussed. Not enough serotonin accompanies depression, excessive carbohydrate cravings, sleep troubles, anger control issues, migraines, irritable bowel syndrome, fibromyalgia, obsessive-compulsive disorder, and an increase in suicide related thoughts and acts.
(Boeree, CG., 2009) (Morris, C., et al., 2004)

The goal of psychopharmacology is to help regain proper balance in the chemistry of the brain, and restore optimal functioning. The use of medications for the mind is therefore, in most instances, directed towards the control of symptoms. Psychiatric medications are not like antibiotics. Medications alone seldom result in a permanent “cure” of mental or emotional troubles. This means in effect that most psychiatric type medications will need to be taken or be available over an extended period of time while other treatments or therapy seek a resolution to the problem causing the symptoms.

Antianxiety Agents

Antianxiety agents are the most commonly prescribed psychoactive drug in the United States. In the adult population, roughly 12.5 percent use a prescribed anxiety medication during the course of a year, while 2 percent of the population will utilize antianxiety medication on any given day (Sola, C., et al., 2010).

Medications that effect brain chemistry in such a manner that they lessen or alleviate anxiety are antianxiety agents. These chemicals may be referred to by terms such as; anxiolytics, sedatives, sedative-hypnotics, or minor tranquilizers. Prescription sleep aids are so closely related to antianxiety medications that they are firmly in the realm of psychopharmacological study and use. Barbiturates and benzodiazepines, along with a loose assortment of other prescription chemicals traditionally form the antianxiety group. In recent years, barbiturates have fallen from use in areas other than induction of anesthesia leaving the benzodiazepines as the mainstay anxiolytic (DuPont, R., et al, 2009).

Sedatives vs. Hypnotics
Sedative - a sedative lowers excitement and calms the awake patient Hypnotic - a hypnotic produces drowsiness and promotes sleep
Sedatives and Hypnotics are by tradition categorized into a single class because of their common ability to induce a state resembling relaxation, sedation and sleep.
(DuPont, R., et al, 2009)

Anxiety medication can be very useful in treating the symptoms that accompany anxiety disorders and often find use in combination with other forms of treatment, such as cognitive-behavioral therapy. The use of anxiolytics help to ease symptoms so that therapy focused on underlying causation may move forward.

It is important to remember that in the treatment of mood, memory or cognitive function, individualization of care requires selection of the best pharmacologic agent for that person. Due to the type of effects, both primary and secondary, that psychiatric medications have on brain chemistry the best fit in treating a particular person for anxiety will not always be an “antianxiety” medication.

Benzodiazepines

The family of medications known as the benzodiazepines is the heart of anxiolytic, or antianxiety treatment. Benzodiazepines are not a cure for anxiety. Their purpose is that of short-term, symptomatic, adjunctive treatment while other lasting solutions are sought for the core issues creating the anxiety.

Psychiatric Reasons to Consider Using Antianxiety Agents
  • Generalized Anxiety Disorder 
  • Social Phobia
  • Acute Stress Disorder
  • Posttraumatic Stress Disorder
  • Panic Disorder
  • Insomnia
  • Agitation
  • Substance Withdrawal

Benzodiazepine-Related Medications

The recent development of new medications, which seem to act on brain benzodiazepine receptor sites without being true benzodiazepine chemicals, opens another path of potential future treatment of anxiety. The FDA currently approves three benzodiazepine-related medications (zolpidem, zaleplon, eszopiclone) for the treatment of insomnia.

Buspirone

Buspirone (Buspar) is a dopamine (D2 receptor) blocking medication approved for use by the FDA for the treatment of generalized anxiety disorder. Structurally different from the benzodiazepines, buspirone can be used for long periods with no potential for abuse, dependence, or tolerance. What buspirone lacks is the quick onset associated with many of the other antianxiety medications. Several weeks of daily dosing is required to achieve anxiolytic benefits.

Anxiolytic Neurophysiology

Gamma aminobutyric acid (GABA) is a key neurotransmitter associated with anxiety. Medications such as the benzodiazepine’s (e.g. Valium, Ativan, etc.) and the barbiturates interact with the availability or reception of GABA in the central nervous system. Benzodiazepine medications bind to neurotransmitter receptor sites BZ1 and BZ2 (benzodiazepine receptor sites 1, and 2) and potentiate the effects of GABA. BZ1 is thought to be closely associated with sleep function, while BZ2 influences cognitive, sensory, motor and memory abilities.

In general, benzodiazepines are equally effective. Drug choice should be based on individual concerns such as how long it takes to reach effect and how long the effect is desired.

Benzodiazepine Antianxiety Medications
Name (Generic) Brand Name Onset (Oral) Duration
Alprazolam Xanax Intermediate Intermediate
Chlordiazepoxide Librium Intermediate Long
Clonazepam Klonopin Fast Long
Clorazepate Tranxene Fast Long
Diazepam Valium Fast Long
Halazepam Paxipam Intermediate Long
Lorazepam Ativan Intermediate Short
Oxazepam Serax Slow Short
Prazepam Centrax Slow Long
Benzodiazepine Medications Used for Insomnia
Flurazepam Dalmane Intermediate Long
Quazepam Doral Fast Long
Temazepam Restoril Intermediate Short
Triazolam Halcion Intermediate Short
Benzodiazepine-Related Medications
Eszopiclone Lunesta Very Fast Short
Zaleplon Sonata Very Fast Short
Zolpidem Ambien Very Fast Short
(DuPont, R., et al, 2009)

Antidepressants

Pharmacologic agents that affect the brain chemistry in such a way as to lift mood or diminish the symptoms of depression are known by the term antidepressant. Clinical depression is widely believed to be the result of functional imbalance in the endogenous neurotransmitters of the brain associated with mood (e.g. serotonin, dopamine, norepinephrine).

The reasons for such imbalance may be on the supply side (i.e. not enough of the correct neurotransmitter is being made), or it may originate on the receiving side (not enough specific receptor sites are available). There may be some unanticipated factor interfering with the function of the neurochemical message system such as malformation of the neurotransmitter molecule, blockage by a third party neurochemical or pseudo-neurochemical, etc. In most instances the exact cause is never known, creating the neurohormonal imbalance which results in a given individuals depression. What is known is that when one antidepressive agent fails, there are options that include antidepressants that work by different mechanisms.

Several classes of antidepressant medication exist, grouped together by the neurotransmitter they primarily affect. Antidepressant groupings include;

  •   Monoamine Oxidase Inhibitors   
  •   Norepinephrine Dopamine Reuptake Inhibitor   
  •   Selective Serotonin Reuptake Inhibitors   
  •   Serotonin Modulators   
  •   Serotonin Norepinephrine Reuptake Inhibitor   
  •   Tricyclic Agents

Antidepressants do not work overnight, and may not work at all. Around 30 percent of clients prescribed antidepressants have no response. Approximately 20 percent have a response, yet stop taking the medicine due to undesired effects. On average only 40 percent of those prescribed an antidepressant show response to the first choice of antidepressant, leading to further medication trials in an effort to match an agent with their biochemical needs (Katon, W., et al., 2010).

Biochemical availability of the pharmacologic agent may occur within hours after taking the first dose. It may however take weeks before the positive effect of the antidepressant is apparent. One theory as to why there is a delay of symptom relief is that complex changes must occur within neurotransmitter receptor sites in the brain before significant symptomatic change can be observed. The belief is that the presence of antidepressant medications promotes change in brain protein production at a cellular level leading to an increase in synaptic plasticity, perhaps even encouraging slow progress toward a healthier brain. What it means in the short term is that therapeutic support of the person in depression is essential, given the slow onset of medication effect (Hirsch, M, et al., 2009).

Monoamine Oxidase Inhibitors

Neurotransmitters chemically tend to be monoamines. Monoamine oxidase is an enzyme that breaks down neurochemicals such as serotonin, dopamine, and norepinephrine. Medication that inhibits the degradation of these neurotransmitters promotes higher levels of mood by increasing the quantity of available neuroactive chemicals.

MAOIs, as monoamine oxidase inhibitors are commonly referred to, were the first class of antidepressants to see clinical use, following their discovery in 1952. MAOIs are effective yet currently not a first-line drug due to a range of severe food-drug and drug-drug interactions that accompany them (Hirsch, M., et al., 2010).

Monoamine Oxidase Inhibitor Interactions
Food Interactions
(Tyramine containing foods)
Drug Interactions
  • Aged cheese
  • Aged, smoked, or pickled meats
  • Yeast extracts
  • Wine (red more than white)
  • Beer
  • Avocado
  • Sauerkraut
  • Caffeine
  • Chocolate
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Meperidine
  • Dextrmethorphan
  • Sertraline
  • Sumatriptan
  • Linezolid
  • All serotonergic agents
Interaction symptoms are similar and represent the effects of excessive catecholamine neurotransmitters in the body: Hypertension, Tachycardia, Tremors, Hyperthermia, and Seizures.
(Bhalla, R., et al., 2010) (Marcus, S., 2009)

MAOIs have been found to be effective in a broad range of anxiety and mood disorders, especially depression. However due to the risk of hypertensive crisis practitioners must be very selective in who they prescribe MAOIs to. The client must be able to understand potential risks and follow a very strict, low-tyramine diet.

MAOIs are very useful in the treatment of “atypical” depression (e.g. depression with hyperphagia, hypersomnia, leaden paralysis, or rejection sensitivity). Clinicians should also consider the MAOIs for use in clients exhibiting treatment resistant depression (Hirsch, M., et al., 2010).

Monoamine Oxidase Inhibitors
Name (Generic) Brand Name Elimination Half-life (hours) Dietary Restrictions
Phenelzine Nardil 1.5-4 Yes
Tranylcypromine Parnate 1.5-4 Yes
Selegiline
(transdermal patch)
Emsam 1.2 No – however caution advised if exceeding recommended dosages
(Hirsch, M., et al., 2010)

Norepinephrine Dopamine Reuptake Inhibitors

Bupropion is an antidepressant distinctly different from the others. Chemically its structure resembles that of amphetamines and has the ability to increase available levels of the “brain reward” neurotransmitter dopamine. A spotty past has led to some hesitancy among prescribers. Bupropion was withdrawn from the market for a short time in the mid 1980’s subsequent to reports of a slightly higher incidence of seizures amongst bulimia clients. In 1989, bupropion returned to the market with a warning to avoid use in clients with a history of anorexia, bulimia, or seizure disorder (Hirsch, M., et al., 2009).

Norepinephrine Dopamine Reuptake Inhibitors
Name (Generic) Brand Name Starting dose, mg/day Usual dose, mg/day
Bupropion Wellbutrin 75-150 300-450
Bupropion SR Wellbutrin SR 100 300-400
Bupropion XL Wellbutrin XL 150 300-450
(Katon, W., et al., 2010)

Selective Serotonin Reuptake Inhibitors and Serotonin Modulators

Serotonin abnormalities are linked to many emotional and behavioral disorders including mood disorders, obsessive-compulsive disorder, and aggressive behaviors. The selective serotonin reuptake inhibitors (SSRIs) have the ability to effectively increase the amount of available serotonin within the brain. Increased levels of serotonin occur quickly after initiation of medication therapy. Initial medication response may be seen in about two weeks, however full effect may not be observed for up to eight weeks from initiation of treatment.

Overall efficacy between the SSRIs in relieving depression appears similar. Choice of agent should be determined by matching medication characteristics with individual need.

Selective Serotonin Reuptake Inhibitors
Name (Generic) Brand Name Starting dose, mg/day Usual dose, mg/day
Citalopram Celexa 10-20 20-60
Escitalopram Lexapro 10 10-20
Fluoxetine Prozac 10-20 20-60
Fluvoxamine Luvox 50 50-300
Paroxetine Paxil 10-20 20-60
Paroxetine CR Paxil CR 12.5-25 25-75
Sertraline Zoloft 50 50-200
Serotonin Modulators
Nefazodone Serzone, Nefadar 50 300-600
Trazodone Desyrel 50 75-300
(Katon, W., et al., 2010)

Serotonin modulators (e.g. nefazone, trazodone) are similar to SSRIs in effect though they operate by a slightly different mechanism. Special caution is indicated when liver damage is present due to the manner in which the body metabolizes these agents.

In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory concerning antidepressants and a possible increase in the risk of suicidal thinking. The following year FDA advisors suggested that concern was justified particularly in children and adolescents taking SSRIs, and recommended a “black box” warning label for all antidepressants to remind prescribers of the risk of increasing suicidal thinking and behavior. Those following the black box issue note that while a slight decrease in treatment of depression may have resulted, what did not occur was an increase in monitoring of clients treated with antidepressants (Andrew L., 2010).

Serotonin Syndrome
Serotonin syndrome is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system
  •    The majority of cases of serotonin syndrome present within 6 to 24 hours of a change or initiation of a drug   
  •   Serotonin syndrome is a clinical diagnosis based on observation as no laboratory test is available to confirm the diagnosis   
  •   Typical vital sign abnormalities include;
    •   Tachycardia and hypertension,   
    •   Severe cases may develop hyperthermia and rapid, dramatic swings in pulse and blood pressure
  •   Physical examination findings include;
    •   Hyperthermia, agitation, ocular clonus (rapid repetitive contractions and relaxations in a muscle), tremor, akathisia (uncontrollable limb and body movements), deep tendon hyperreflexia, inducible or spontaneous clonus, muscle rigidity, dilated pupils, dry mucus membranes, increased bowel sounds, flushed skin, and diaphoresis
 
  •    Treatment of serotonin syndrome includes;
    •   Discontinuation of all serotonergic agents 
    •   Supportive care aimed at normalization of vital signs   
    •   Sedation, usually with benzodiazepines   
    •   Possible administration of serotonin antagonists (e.g. Cyproheptadine, a histamine-1 receptor antagonist)
(Boyer, E., 2010)

Serotonin Norepinephrine Reuptake Inhibitor

Combining the “high alert” system arousal effects of increased norepinephrine with the positive mood benefits of serotonin may be a good combination for some clients struggling with depression. The serotonin norepinephrine reuptake inhibitors (SNRIs) tend to also have a weak dopamine reuptake effect. Safety and tolerability of the SNRIs are similar to the SSRIs, although monitoring is warranted for an uncommon sustained rise in blood pressure (Bhalla, R., et al., 2010).

Serotonin Norepinephrine Reuptake Inhibitors
Name (Generic) Brand Name Starting dose, mg/day Usual dose, mg/day
Desvenlafaxine Pristiq 50 50 (no titration)
Duloxetine Cymbalta 30 60-120
Venlafaxine Effexor 37.5 75-300
Venlafaxine XR Effexor XR 37.5 75-300
Noradrenergic and Specific Serotonergic Antidepressant
Mirtazapine Remeron 15 15-45
(Katon, W., et al., 2010)

Mirtazapine (Remeron) is an antidepressant without a home. It is neither an SSRI nor is it an SNRI. Its effects are similar, yet subtly different than either grouping and because of those differences, it should be considered as an option in clients with treatment resistant depression who are not responsive to SNRI or SSRI medications (Katon, W., et al., 2010).

Another odd medication is Milnacipran. This is a relatively new SNRI, but with a twist. It is currently approved by the FDA for use in the treatment of fibromyalgia, but not for use in depression (Hirsch, M., et al., 2009).

Case Study:
A 36-year-old dental hygienist is transported to the emergency department after collapsing at work. She exhibits as awake though slightly confused, with visible hand and arm tremors, dilated pupils, dry lips, flushed face, and diaphoretic. BP 186/98, P 114, R 26, T101.

On interview, she states she had just been to see her primary physician earlier in the week and had been fine except for some ongoing depression that was not improving. Further questioning reveals she had received a new prescription, for an SRNI antidepressant and had taken the first dose yesterday, without first weaning off the SSRI antidepressant she had previously been prescribed.

Tricyclic Antidepressants

Cyclic antidepressants were discovered in the 1950’s. The first cyclic antidepressants were named “tri”-cyclic because their chemical structure somewhat resembled three interlocked rings when drawn out in scientific notation. Several other cyclic formulations have been discovered since the days of the three-ringers; however tradition carries the name tricyclic forward for the general grouping despite its current descriptive inaccuracy (Hirsch, M. & Birnaum, R., 2010).

Cyclic antidepressants find less common use than the current first-line SSRI and SNRI agents. This in part is due to a wider neurotransmitter effect, with more brain chemicals being shifted and a resultant broadening of potential side effect profiles.

Cyclic Antidepressants
Name (Generic) Brand Name Starting dose, mg/day Usual dose, mg/day
Amitriptyline Elavil 25-50 100-300
Amoxapine Asendin 50 100-400
Clomipramine Anafranil 25 100-250
Desipramine Norpramin 25-50 100-300
Doxepin Adapin, Sinequan 25-50 100-300
Imipramine Tofranil 25-50 100-300
Maprotiline Ludiomil 50 100-225
Nortriptyline Pamelor 25 50-200
Protriptyline Vivactil 10 15-60
Trimipramine Surmontil 25-50 100-300
(Katon, W., et al., 2010)

The cyclic antidepressants have been associated with occasional cardiac problems. It is highly recommended that before prescribing any of the cyclic agents a baseline electrocardiogram (ECG) and cardiac history be conducted. In younger clients (less than 40) with a negative cardiac history the ECG may not be warranted (Hirsch, M. & Birnaum, R., 2010).

Antipsychotics

Antipsychotic medications have been around for more than 50 years. These pharmacologic agents affect many neurotransmitter systems and while most often are thought of as treatment for symptoms of schizophrenia, they have effect against psychosis irrespective of cause. Depending on the individual, antipsychotics may be of benefit for manic episodes, agitation, delirium, and as augmentation therapy for other psychiatric conditions.

Generally speaking all antipsychotics are equally effective when given at an adequate dose for a sufficient length of time. Please be aware that with these powerful psychopharmaceuticals there will be a wide range of variability in individual client response and sensitivity to unwanted adverse medication effects. This means that for practical purposes the most important considerations in choice of antipsychotic agents to for use in treatment are;

  •   Previous experience that this client has had with antipsychotics   
  •   Experience that a close relative has had with antipsychotics   
  •   Side effect profile of individual antipsychotic agents

Antipsychotic medications are divided into three categories. Typical antipsychotics (aka neuroleptics, conventional antipsychotics, major tranquilizers) tend to refer to older "first-generation" drugs. Atypical antipsychotics are comprised of newer "second-generation" agents with a narrower pattern of unwanted effects. Finally there is Clozapine, a somewhat unusual medication with some unique antipsychotic properties which forms a very small group all its own.

The mechanism of action of antipsychotics is complex. What is shared in common is that all antipsychotic medications interact with the metabolism of the neurotransmitter dopamine, the subtype of dopamine referred to as D2 in particular. Each of the antipsychotics varies in the degree to which D2 is affected. They also vary as to the other neurotransmitters they either boost or inhibit. Serotonin, histamine, glutamate, and GABA, along with other neurotransmitters all play a role in the symptoms of psychosis and schizophrenia. Because of this intricacy of discord in the chemistry of the brain, identifying the best antipsychotic to diminish an individual person's symptoms that has the least unwanted effects is something of an art form.

Both atypical and typical antipsychotics are effective in the management of the positive symptoms of schizophrenia. Atypical drugs have a greater effect on the negative symptoms of schizophrenia.

Positive Symptoms of Schizophrenia Negative Symptoms of Schizophrenia
  • Agitation
  • Tension
  • Insomnia
  • Verbal incomprehensibility
  • Bizarre behavior
  • Hallucinations
  • Delusions
  • Paranoia
  • Social withdrawal
  • Lack of motivation
  • Flat or blunted effect
  • Anhedonia (lack of pleasure)
  • Poor hygiene and grooming
  • Limited spontaneous conversation
  • Poor social skills

Typical Antipsychotics

Older, first-generation drugs remain a valuable resource. They are characterized by good efficacy, however has a higher incidence of Parkinson's disease-like neuromuscular symptoms (pseudoparkinsonism) and EPS (extrapyramidal side effects). EPS effects include such things as slow and diminished movements (bradykinesia), tremors, rigidity, subjective and objective restlessness (akathisia). Typical antipsychotics also carry a risk of developing a lasting choreoathetotic (spasmodic irregular) movement disorder known as tardive dyskinesia.

Further unwanted effects common to typical antipsychotics are the elevation of serum prolactin, a risk of a cardiac rhythm effect known as QT prolongation, feelings of sedation, and anticholinergic effects (Jibson, M., 2009).

Typical Antipsychotics with Side Effect Profile
Generic Brand Name Sedation EPS Orthostatic Hypotension Anticholinergic
Chlorpromazine Thorazine High Low High Moderate
Thioridazine Mellaril High Low High High
Mesoridazine Serentil Moderate Moderate High High
Molindone Moban Moderate High Moderate Moderate
Perhenazine Trilafon Low High Moderate Low
Loxapine Loxitane Moderate High Moderate Moderate
Trifluoperazine Stelazine Moderate High Low Low
Thiothixene Navane Low High Low Low
Fluphenazine Prolixin Low Very High Low Low
Haloperidol Haldol Low Very High Very Low Very Low

Atypical Antipsychotics and Clozapine

Second-generation drugs are often the first choice in treatment for psychotic symptoms. They have a lower incidence of unwanted EPS as well as a reduced risk of tardive dyskinesia. What they lack however, is a firm record of superior performance over the older typical antipsychotic agents. Which brings the realization that for any particular client, newer may not be superior to older. Treatment choices should be based on factors such as individual client response, side effect profile, and cost (Jibson, M., 2009).

Atypical Antipsychotics Side Effect Profile
Generic Brand Name Sedation EPS Orthostatic Hypotension Anticholinergic
Aripiprazole Abilify Low Low Low None
Olanzapine Zyprexa Moderate Very Low Low Low
Paliperidone Invega Low Low Moderate Very Low
Risperidone Risperdal Low Low Moderate Very Low
Quetiapine Seroquel Moderate Very Low Low Very Low
Ziprasidone Geodon Very Low Low Low None
Clozapine Side Effect Profile
Clozapine Clozaril Very High Very Low High High

Atypical antipsychotics and clozapine have been associated with an increase in metabolic syndrome (e.g. hyperglycemia, dyslipidemia, and hypertension) as well as an increased risk of new onset diabetes. Weight gain is also a significant issue with atypical agents, with clozapine and olanzapine having the greatest reports of increase.

Clozapine

Clozapine is a stand-alone antipsychotic. It affects the dopamine D2 receptor sites, as do all of the antipsychotic medications. Clozapine is prized for its history of good effect on the 30-percent of schizophrenic clients whose metabolism resists antipsychotic treatment. In fact, in this group some 30 to 50 percent show significant improvement in symptoms once started on clozapine (Jibson, M., 2009).

The bad news however, and the reason why clozapine is not a first-line antipsychotic, is not the adverse effects of weight gain and risk of metabolic syndrome. It is the presence of an unusually high risk of agranulocytosis. This abnormally low level of white blood cells in the body (agranulocytosis) occurs in between 1 and 2 percent of clients during their first six months of treatment and can occur even later into the treatment, though at a less frequent rate. The FDA requires practitioners' prescribing clozapine to weekly monitor white blood cell counts (WBC) for the first six months, then biweekly for the next six months. After that, WBC checks can be every four months for the duration of treatment.

Mood Stabilizers

Mood stabilizers are medications that buffer the dramatic emotional rollercoaster ride which often accompanies bipolar affective disorder. The term mood stabilizer applies to medications that alleviate the intensity or the frequency of depressive, hypomanic, manic or mixed episodes in clients with bipolar affective disorder (aka manic-depression). Mood stabilizers are the mainstay treatment for acute mania. They are used to induce remission in those individuals experiencing symptoms of hypomania, manic episodes, and aid to stabilize mood swing cycles into a maintenance range closer to what that person's normal would be.

Lithium and a select group of antiepileptic medications form the mood stabilizers. Studies of these agents have similar response rates, of between 50 to 60 percent, in clients with acute mania. Choice of agent therefore revolves around previous experience for the client, comorbid medical conditions that are present, and side effect profiles of the drug (Stovall, J., 2010).

Lithium in particular has a tricky set of potential adverse effects, starting with the renal system. Clients with compromised renal function may not be able to excrete lithium efficiently and therefore are at risk for lithium intoxication. Common side effects of lithium therapy include polyuria, loose stools, tremor, cognitive effects such as confusion, and weight gain. Around 10 to 20 percent of clients on lithium therapy develop hypothyroidism. Tremors are so common with lithium that up to 65 percent of clients will experience them to an extent. Sudden worsening of an existing tremor or sudden appearance of a tremor that had not previously been present can be a sign of impending lithium toxicity (Stovall, J., 2010) (Saxena, S., et al., 2007).

The alternative mood stabilizers are closely related to the antiepileptic medication family, and also require careful monitoring. Carbamazepine for example may cause dose-related diplopia (double vision) or ataxia (the inability to coordinate muscle movements). Lamotrigine may cause nausea, skin rash, dizziness, or headache. Valproic acid can cause liver problems, gastrointestinal distress, weight gain, and even alopecia (hair loss). Oxcarbazepine is associated with sodium loss and can cause hyponatremia as well as somnolence, dizziness, nausea, or dizziness.

It is unclear how mood stabilizers work. Current thought is that they are able to alter the ion channels of cell walls in the central nervous system. Many also increase available GABA levels.

Mood Stabilizers
Name (Generic) Brand Name Normal Serum Level Weight Effect
Carbamazepine Epitol, Tegretol 4-12 mcg/mL Neutral
Divalproex sodium Depakote 50-125 mcq/mL Increase
Lamotrigine Lamictal n/a Neutral
Lithium carbonate Eskalith, Lithobid 0.5-1.2mEq Increase
Oxcarbazepine Trileptal n/a Neutral
Valproic acid Depakene 50-125 mcq/mL Increase
(Minirth, F., 2010) (Stovall, J., 2010)
Case Study:
Harold Jennings is a 43-year-old construction worker. He drove himself to the emergency room after work complaining of an extensive skin rash that had developed over the course of three to four days. He also reports feelings of gastric upset, a lingering headache, and fatigue. Physical inspection shows a large area of reddened, raised tissue on the back of one hand, up the dorsal aspect of the forearm, and a second extensive area of discoloration in the mid-back region.
Mr. Jennings reports that he has no allergies. He is physically in good health and visits a medical clinic twice a year for checkups for manic-depressive disorder that he currently has in remission.
On questioning Mr. Jennings relates that he had a medication change at his last clinic visit, from Lithium to Lamotrigine, six weeks ago.

Psychostimulants

Psychostimulants affect the dopaminergic and noradrenergic neurotransmitter systems, causing the release of catecholamines from storage sites at the central nervous system (CNS) synapses. Psychostimulants reduce feelings of fatigue, promote alertness and wakefulness, increase ability to concentrate, and have possible mood enhancing properties. In current psychiatric practice, their use is largely limited to attention deficit and sleep disturbance disorders such as narcolepsy (Krull, K., 2009).

Historically attention deficit hyperactivity disorder (ADHD) and attention deficit disorder (ADD) were believed to be a time-limited condition of childhood. New data suggests that between 30 to 70 percent of children affected continue to manifest symptoms in adulthood and that between 1 and 7 percent of the adult population experience significant ADHD symptoms (Searight, H., et al., 2010).

The mainstay treatment for attention deficit conditions is pharmacotherapy. This is true for both children and adults. Currently one third of all stimulant prescriptions for attention deficit are written for adult clients, which represents a 90 percent jump in adult psychostimulant therapy from the year 2002 to 2005 (Searight, H., et al., 2010).

Available studies fail to show improvement in school performance in children to whom psychostimulants have been prescribed, however the use of stimulant medication has in studies demonstrated improved behavior in all children to whom they are given (e.g. children with ADHD, learning disabilities, depression, and even normal children), not just those with ADHD. Adults report an increase in ability to concentrate while taking prescription psychostimulants (Krull, K., 2009) (Searight, H., et al., 2010).

Psychostimulants
Name (Generic) Brand Name Used in Children Used in Adults
Dexmethylphenidate Focalin Yes Yes
Methylphenidate Ritalin, Methylin Yes Yes
Dextroamphetamine Dexedrine, Dextrostat Yes Yes
Amphetamine mixed salts Adderall Yes Yes
Related Medications
Atomoxetine Strattera Yes Yes
(Krull, K., 2009) (Searight, H., et al., 2010)

Atomoxetine (Strattera) is a non-stimulant approved for use in children older than six years of age, adolescents, and adults diagnosed with ADHD. It is not a true psychostimulant. Instead, it is more closely related to the SNRI medications. Despite a different mode of action it has stimulatory effects on the sympathetic nervous system and been well received as a psychotherapy alternative, especially in instances where there exists a potential for abuse.

Summary

Psychopharmaceuticals are valuable tools in the treatment of mental illness. Psychiatric medications help control symptoms and are a beneficial adjunct to other forms of therapy. The use of prescription medications to alter brain chemistry and function, seeking clarity of thought and focus. The prevalence of these helpful and therapeutic medications creates a need for awareness among health professionals concerning the basics related to psychoactive pharmacology, the medications for the mind.

References

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Marcus, S. (2009). Toxicity, Monoamine Oxidase Inhibitor. eMedicine.com. Retrieved April 14, 2010, from (Web Site).

Minirth, F. (2010). Bipolar Disorder Part II, Mood Stabilizers. Retrieved April 26, 2010, from (Web Site).

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Sola, C., et al. (2010). Sedative, Hypnotic, Anxiolytic Use Disorders. eMedicine.com. Retrieved April 4, 2010, from (Web Site).

Stovall, J. (2010). Bipolar Disorder Treatment of Acute Mood Episodes. In: Hirsch MS (Ed.) UpToDate 18.1. Waltham, MA.

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This course is applicable for the following professions:

Advanced Registered Nurse Practitioner (ARNP), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Registered Nurse (RN)

Topics:

Advance Practice Nurse Pharmacology Credit, CPD: Practice Effectively, Pharmacology, Psychiatric


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