Psychotherapeutic Agents To understand psychotherapeutic agents we must understand the Central nervous system(brain and spinal cord). This system must be able to process and respond quickly to external and internal activity. While maintaining homeostasis through visceral, somatic and motor activity it must also create and respond to memories, thoughts, and emotions every second of the day.


Psychotherepeutic agents must be able to alter CNS diseases or disorders like, anxiety, schizophrenia, parkinson's disease, mental disorders, and epilepsy. Some drugs that are used are, Opioids, Benzodiazepines, Local Anesthetics, Antihypertensives, Inhalation anestheitics, Antiparkinsons agents and Antipsychotics. Some of the devisions of the CNS include the, Cerebral Cortex, Limbic System, Midbrain and Brainstem, and Spinal Cord. The Cerebral Cortex: Somatosensory cortex processes sensory information. Motor Cortex initiates and coordinates somatic muscle activity. Association/Visual/auditory areas are involved with voluntary movement, integration of sensation, consciousness, abstract thought, memory and learning. Drugs that alter the Cerebral Cortex Activityb by reducing cortical activity.

Antianxiety drugs = Benzodiazepines, such as (Diazepam) used to manage anxiety disorders, ethanol withdrawal, skeleta muscle relaxant and treatment of convulsive disorders. Benzodiazepines also effect the Limbic system. Benzodiazepines also can act on different sites within this system to activate or make more effecive the production of GABA(Y-aminobutyric acid)which will help reduce anxiety and development of sedation.




Limbic System(amygdala, septum, hippocampus, olfactory lobes, basal ganglia and portions of the thalamus) coordinate emotional sensations with motor visceral and endocrine functions.
Benzodiazepines help modify this system.
Schizophrenia may have excessive dopaminergic activity and drugs used to treat this psychotic episode must be a dopamine receptor antagonist to block the excess dopamine being processed.

Just the opposite with Parkinson's Disease which has a major decrease in dopaminergic activity and treated with drugs such as Levodopa to increase the generation of Dopamine.

Epileptic patients have a reduction of Benzodiazepine receptors which could be a part of the pathogenesis o epliepsy.

Midbrain and Brainstem(mesencephalon, pons, medulla, retiicular activating system and most of the cranial nerve nuclei):

coordinates cardiovascular, pulmonary and gastrointestinal systems. Integrates swallowing and vomiting reflexes. Maintains arousal and development of sleep.

This system is sensitive to many drugs and CNS depressants.
Opioids can produce anlgesia by activating opioid receptors.

diagnosis of depression references the American Psychiatric Association Criteria for Diagnosis of Major Depression: (alyssa) At least five of the following symptoms must be present within a two week period. At least one symptoms must be depressed mood or loss of interest or pleasure.
  • Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g. feels sad or empty) or observation made by others (e.g., appears tearful) Note: In children and adolescents, this can be irritable mood.
    • Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day, as indicated by either subjective account or observation made by others).
    • Significant weight loss (when not dieting) or weight gain (e.g., a change of more than 5% of body weight in a month) or decrease or increase in appetite nearly every day. Note: in children, consider failure to make expected weight gains.
    • Insomnia or hypersomnia nearly every day.
    • Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
    • Fatigue or loss of energy nearly every day.
    • Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guild about being sick).
    • Diminished ability to think or concentrate or indecisiveness, nearly every day.
    • Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan or a suicide attempt or specific plan for committing suicide.

[Source: Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC; America Psychiatric Association, 1994]; Boyer, W., and Nemeroff, C.B., Mood Disorders: Depression and Mania, In, Medicine for the Practicing Physician, (Hurst, J.W., editor-in-chief) Appleton and Lange, 1996, pp. 22-2


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Definitive diagnosis of mania references the American Psychiatric Association Criteria for Diagnosis of Mania

  • A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least one week (or any duration if hospitalization is necessitated)
  • During the period of mood disturbance, three (or more) of the following symptoms have persisted (for if the mood is only irritable) and have been present to a significant degree:
  1. Inflated self-esteem or grandiosity.
  2. Decreased need for sleep (e.g. feels rested after only 3 hours of sleep)
  3. More talkative than usual or pressure to keep talking.
  4. Flight of ideas or subjective experience that thoughts are racing.
  5. Distractibility.
  6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation.
  7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g. engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments.
Mood disturbances must be sufficient to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

Treatment of Manic Patients:
Although manic disorder or bi-polar disorder, is thought to have a genetic component, it is treatable with anti-manic drugs.

Lithium Salts: These are used in the treatment of mania but, are only adequat for about half of the diagnosed conditions.
It is thought that these can be useful as a prophylactic in unipolar and bi-polar disorders and as prevention for the degenerative disese of

Antipsychotic Drugs: These are used in 85% of patients during the initial stage of therapy.

Anti-Convulsants: The use of valproate and carbazepine along with, omega -3 fatty acids, calcium channel blockers, thyroid stimulating hormone, and
thyroid hormone have recently been introduced as adjuncts to traditional bipolar disorder therapy.

benzodiazepines: The use of clonazepam and lorazepam in conjunction with haloperidol. have proven effective to calm down manic patients until lithium can
achieve a therapeutic concentration.

Major types of antidepressants include:

  • Tricyclic antidepressants (TCAs) are some of the first antidepressants used to treat depression. They primarily affect the levels of two chemical messengers (neurotransmitters), norepinephrine and serotonin, in the brain. Although these drugs are effective in treating depression, they have more side effects, so they usually aren't the first drugs used.
  • Monoamine oxidase inhibitors (MAOIs)are another early form of antidepressant. These drugs are most effective in people with depression who do not respond to other treatments. They are also effective for other mental illnesses. Substances in certain foods, like cheese, beverages like wine, and medications can interact with an MAOI, so these people taking this medication must adhere to strict dietary restrictions (see below). For this reason these antidepressants also aren't usually the first drugs used.
  • Selective serotonin reuptake inhibitors (SSRIs) are a newer form of antidepressant. These drugs work by altering the amount of a chemical in the brain called serotonin.
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs) are another newer form of antidepressant medicine. They treat depression by increasing availability of the brain chemicals serotonin and norepinephrine.

Examples of effective and safe medications commonly prescribed for depression or depression-related problems are listed in the chart below.

Drug Name
Type of medication
Potential Side Effects

These medicines are tricyclic antidepressants (TCAs) which work by increasing the available amount of serotonin and/or norepinephrine in the brain.
Dry mouth, blurred vision, increased fatigue and sleepiness, weight gain, muscle twitching (tremors), constipation, bladder problems such as urine retention, dizziness, daytime drowsiness, increased heart rate, sexual problems.

Monoamine oxidase inhibitors (MAOIs) increase the amount of norepinephrine and serotonin in the brain
Must avoid certain foods and medications to avoid dangerous interactions*
Serious side effects may include: headache, heart racing, chest pain, neck stiffness, nausea and vomiting. If you experience any of these symptoms, seek medical care immediately.


Selective serotonin reuptake inhibitors, or SSRIs, work by increasing the amount of serotonin, a neurotransmitter found in the brain.
Sexual problems including low sex drive or inability to have an orgasm are common but reversible, dizziness, headaches, nausea right after a dose, insomnia, feeling jittery.
Wellbutrin may increase the amounts of the neurotransmitters norepinephrine and dopamine in the brain.
Weight loss, decreased appetite, restlessness, insomnia, anxiety, constipation, dry mouth, diarrhea, dizziness
Wellbutrin is much less likely to cause the weight gain or sexual problems seen with other antidepressants.


These drugs increase the levels of the neurotransmitters serotonin and norepinephrine in the brain.
Drowsiness, blurred vision, lightheadedness, strange dreams, constipation, fever/chills, headache, increased or decreased appetite, tremor, dry mouth, nausea.
Remeron can be sedating. Cymbalta may increase sweating and blood pressure and also cause fatigue and reduced energy.

Desyrel (trazodone)

These drugs block various neurotransmitter chemicals to some degree.
Desyrel may cause drowsiness, fatigue, tremor, headache, dry mouth, nausea and vomiting.
Ludiomil may cause headache, dizziness, dry mouth, fatigue, daytime sleepiness, sweating.


Mechanism of action:
The principal mechanism of action of barbiturates is believed to be their affinity for the GABAA receptor
Barbiturates bind to the GABAA receptor at the alpha subunit, which are binding sites distinct from GABA itself and also distinct from the benzodiazepinebinding site.
Barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS.
Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA receptor (pharmacokinetics: this increases the efficacy of GABA) whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA receptor (pharmacokinetics: this increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to
benzodiazepines in overdose
Tolerance and dependence
With regular use tolerance to the effects of barbiturates develops. This in turn may lead to a need for increasing doses of the drug to get the original desired pharmacological or therapeutic effect.[17] Barbiturate use can lead to both psychological and physical dependence and the drugs have a high abuse liability.[18] Psychological addiction to barbiturates can develop quickly. The GABAA receptor, one of barbiturates' main sites of action, is thought to play a pivotal role in the development of tolerance to and dependence on barbiturates, as well as the euphoric "high" that results from their abuse.[18] The mechanism by which barbiturate tolerance develops is believed to be different than that of ethanol or benzodiazepines, even though these drugs have been shown to exhibit cross-tolerance with each other.[19]

Pharmacological effects:


Depression to varying degrees ranging from mild sedation--- respiratory arrest--- death.
Many factors affect the level of depression such as:

Drug, dose, route, pt. initial behavior state, environmental surroundings, time taken, physical and psychological state.

CV. system:
-Sedative dose= no effect
- Hypnotic dose= mild hypotension and decrease heart rate
- Beyond hypnotic dose= progressive depression.

Respiratory system:

- At a high dose it caused progressive respiratory depression
- It increases respiratory reflux activity such as coughing sneezing.

Absorption, fate and excretion:
Generally available in Na salt therefore, completely absorbed in GI tract
Lipid solubility determines their crossing of the blood brain barrier.

Stored in the body fat therefore slowly released, metabolized and excreted.
The long term use increases the liver microsomal enzyme activity.

Adverse effect and drug interaction:
Capability to induce hepatic microsomal enzyme.
High dose depressed respiration
Increase respiration complication such as cough and sneezing.
Combination of 2 or more CNS depressant produces an increase in the level of CNS depression
Dentist need to inform their patient to restrict alcohol consumption after general anesthesia.
Obtain accurate MH keep record of the drug, dose and time taken. Consult physician.

Therapeutic uses:
Management of tonic-clonic seizures and other types of convulsive disorders. short acting can be administered as inravenous sedatives and anesthetics

Chlora hydrate: none barbiturate sedative hypnotics

Pharmacological effect:

Sedative hypnotic in pediatric dentistry
Used in TX of alcohol withdrawal

Adverse Rxn

CV depression

Drug interaction:

Causes CNS depression when taken with other sedatives
Combination with alcohol = potentiating drug interaction
It‘s a mutagen that causes chromosomal damage


Pharmacological effect:

- Bronchodialator - inihibit the contraction of gastrointestinal and bronchiol smooth muscle and increase capillary permeablility.
- CNS depressant
- Analgesic
- Decrease in salivary secretion

Absorption, fate, and excertion:

Rapidly absorbed orally or parenterally. Terminated by conversion to inactive metabolites through hydroxlation in the liver. Second generation H1 antihistamines are not metabolized to an active form and are largely excreted unchanged in the urine.

Adverse Reaction

Drowsiness and dry mouth.
General therapeutic uses of sedative Hypnotics

- Relieve fear and anxiety in dental procedure= barbiturates has been supplanted by benzodiazepines
- Chlora hydrates and antihistamine are still in use in pediatric dentistry
- Sleep disorder
- Barbiturates are used in anesthesia and IV sedation to deepen CNS depressant

Uses in Dentistry

-CNS actions rather than for their specific antihistaminic effects. May be used for conscious sedation and general anesthesia. May also be useful when patient is allergic to conventional local anesthetics. or management of systemic anaphylatic reactions that may occur in the dental setting.

Centrally acting muscle relaxant

Pharmacological effect

Relaxation of the voluntary muscles
Reduce the neural activity in variety of brain structure.

Most widely used due to their highly safety margin

Mechanism of action:

- When GABA is activated … the Cl channel opens up allowing for the Cl influx… membrane hyper polarization and neural inhibition.
- It increases the frequency of channel opening
Causes relaxation of voluntary muscles through depression of CNS

  1. Mechanism of action: generally reduce neural activity in a variety of brain structures including brainstem, thalamus and basal muscle relaxation also show some preferential depression of polysynaptic reflex; thus depression of interneurons is not an identifying characteristic of this class.
  2. Although their precise mechanism of action is unknown, the centrally acting drugs don’t relax skeletal muscles directly or depress neuronal conduction, neuromuscular transmission, or muscle excitability. Rather, centrally acting drugs are known to be central nervous system CNS depressants. The skeletal muscle relaxant effects that they cause are likely related to their sedative effects.

Pharmacological effect


- Depression, sedative hypnotic, muscle relaxant, and antiseizure activity.

CV system,:

- Greater than normal dose= decrease in BP, cardiac out put and stroke volume.

Respiratory system:

- Depressant and apnea.

Absorption, fate, and excretions;

Differ, wide range of speed of on set duration:
Short acting, intermediate, long acting
Classified according to their elimination ½ life
After oral administration = rapid absorption
Many biotransform to long acting metabolites which causes the hangover the next day.

Adverse effect:

- Drowsiness
- In elderly and young patient causes excitation rather than depressant
- Change in normal sleep pattern
- Allergic rxn = skin rash
- Dizziness
- Can result in physical and psychological dependence
- Abrupt cessation of these drugs can cause several withdrawal symptoms
- Bradycardia
- Abdominal distress
- Constipation
- Diarrhea
- Heartburn
- Nausea and vomiting

Therapeutic Uses:

- Patient receive these drugs to treat acute, painful musculoskeletal condition
- Used in conjunction with rest and Physical Therapy.

Tolerance and psychological dependence:

- Develop frequently
- Physical dependence depend on the drug dose and ½ life
- Despite this problem it is considered the highest safety margin compared to other sedative drugs.

Drug interaction:

  • Alcohol and other CNS depressants - cause synergistic adverse effects, with possible increase in depression and suicide.
  • Antacidsand anticholinergics- may slow down absorption which may slow down acute therapeutic effects.
  • Oral contraceptives, isoniazid reduces the rate of elimination and thus the half-life increases leading to possibly excessive drug accumulation.
  • CimetidineInhibition of metabolism of benzodiazepines, causing accumulation which especially with long half life benzodiazepines such as diazepam may cause toxic effects.
  • Rifampicin - increases rate of metabolism, thus shortening the elimination half-life of benzodiazepines
  • Digoxin protein binding of diazepam altered causing increased digoxin levels
  • L-dopa - worsening of parkinsonian symptoms
  • Disulfiram - slows down the rate of metabolism leading to increased effects of benzodiazepines.
Benzodiazepine Specifically:
Mechanism of action: Benzodiazapine increases frequency of Cl- channels in response to GABA. Thus any transmitters system modulated by GABA is inhibited to a greater extent by benzodiapines.
As Benodiazepines bind to receptors on or near the GABA receptors, it enhances the effect of the inhibitory neurotransmitter GABA, and allows more cholride ions to flow into the postsyaptic neuron. This depresses the nreve impulses, causing them to slow down or stop.

Pharmacological effects: Effects CNS as depressant and sedative. Anti-anxiety, sedative-hypnotic, amnesic, anticonvulsant and skeletal muscle relaxant properties.

Pharmokenetics: Certain benzodiazapine (alprazolam) has documental antidepressant and anti-panic properties. Diazepam is skeletal muscle relaxant. Diazepam is only benodiazapine approved for treatment of muscle spasm of central origin.
Adverse reactions: Drowsiness, dysarthia, ataxia, confusion, dizziness, muscle weakness, apathy. In elderly and really young, experience paradoxical reactions (the opposite) such as nightmare and insomnia.

Abuse and tolerance: true physical dependence is less common. Severity is dependant on half life of drug.
Tolerance is slower to develop with long acting agents. Quick withdrawal of drug leads to patient feeling increased symptoms that they were originally taking benzodiazapine for ex: anxiety and sleeplessness.

Drug interactions: specific drug interactions include: Carbamaepine, rifampin, Cimetidne, and other antiolytics and other sedative hypnotics. Do not take if patient is pregnant, in large doses or with anti-fungals and antimicrobials.
Lethal Combination when benzodiazepines are taken with other CNS depressants including alcohol and anticonvulsants. The result is enhanced sedative and CNS depressant effects, including reduced level of conciousness, reduced muscle coordination, respiratory depression, and death.
The metabolism of the benzodiazepine - Flurazepam may be reduced by hormonal contraceptives, increasing the risk of toxcity.

Management: Patient should gradually withdraw from drug due to side effects increases with immediate withdrawal from system.

Uses and management of patient: Uses are mainly for anti-anxiety or sedative.
Benzodiazepines should not be given for more than a 4 month period.

Antianxiety Drugs:

  1. Mechanism: Although buspirone’s mechanism of action remains unknown, it’s clear that buspirone doesn’t affect GABA receptors like benzodiazepines. Buspirone seems to produce various effects in the midbrain and acts as a midbrain modulator, possibly due to its high affinity for serotonin receptors.
  2. Therapeutic uses:
o Treat generalized anxiety states
3. Adverse effects:

o Dizziness
o Light headedness
o Insomnia
o Rapid heart rate palitations

Psychoactive drugs can be classified into seven major categories. These include:

  • Antianxiety agents. Drugs used to treat anxiety disorders and symptoms. These include benzodiazepines such as alprazolam (Xanax), lorazepam (Ativan), diazepam (Valium), and chlordiazepoxide (Librium), and other medications including buspirone (Bu Spar) and paroxetine (Paxil).
  • Antidepressants. Prescribed to treat major depressive disorder, dysthymic disorder, and bipolar disorder. Popular antidepressants include venlafaxine (Effexor), nefazodone (Serzone), bupropion (Wellbutrin), MAOI inhibitors such as phenelzine (Nardil) and tranylcypromine (Parnate); selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft); tricyclic antidepressants such as amitriptyline (Elavil), doxepin hydrochloride (Sinequan), desipramine (Norpramin), and perphenazine/amitriptyline combinations (Etrafon).
  • Antimanic agents. This category includes medications used to treat mania associated with bipolar disorder (or manic-depressive disorder) such as divalproex sodium (Depakote) and lithium carbonate (Lithium, Eskalith, Lithobid, Tegrator).
  • Antipanic agents. Prescribed to treat the panic symptoms that are a defining feature of many anxiety disorders. Medications include clonazepam (Klonopin), paroxetine (Paxil), alprazolam (Xanax), and sertraline (Zoloft).
  • Antipsychotic agents. Also known as neuroleptic agents, these medications are used to manage psychosis related to schizophrenia, delusional disorder, and brief psychotic disorder. They include clozapine (Clozaril), haloperidol (Haldol), loxapine (Loxitane), molindone (Moban), thiothixene (Navane), risperidone (Risperdal), and olanzapine (Zyprexa); also includes phenothiazines such as prochlorperazine (Compazine), trifluoperazine hydrochloride (Stelazine), and chlorpromazine (Thorazine).
  • Obsessive-compulsive disorder medications. Drugs used to treat OCD include fluvoxamine (Luvox), paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft).
  • Psychostimulants. Also known as central nervous system stimulants, these medications are used to treat attention deficit disorders (ADD and ADHD) and narcolepsy. They include methylphenidate hydrochloride (Methylin, Ritalin) and methaamphetamines (Desoxyn, Dexedrine, and Dextro Stat).

This drug
interacts with...
to cause...
tricyclic antidepressants
increased effect of antidepressants due to decreased breakdown by liver
peripheral vasoconstriction and may reverse action of epinephrine
decreased effect of antipsychotic due to decreased absorption from GI tract
anticholinergic agents
decreased effect of haloperidol
opoid analgesics
enhanced opiod-induced respiratory depression
sodium bicarbonate
increased effect of tricyclics by increased renal tubular reaborption of drug
Antimanic &
increased effect of benzodiazepines by decreased breakdown by liver
increased effect of benzodiazepines due to decreased breakdown by liver
decreased rate of absorption of benzodiazepines
potentiation of CNS depressant effects.