What are the most important things to consider in administering psychotropic medication?

XII Dissociative Anesthetics

This class of psychoactive drugs includes ketamine and PCP (phenyl cyclohexyl piperidine or phencyclidine). They are synthetic compounds introduced into medicine to produce an anesthetic loss of sensation without depressing respiration and cardiovascular function as do the general anesthetics. Although PCP is no longer used medically, ketamine is used for both human and veterinary surgical procedures. At subanesthetic doses in humans, ketamine produces an altered state of consciousness that has some psychedelic-like characteristics and may be accompanied by a loss of body sensation. The primary neurochemical effect is as an antagonist at the NMDA-type glutamate receptor.

Indications for use

The use of psychotropic drugs is only one of the adjunctive measures available in the comprehensive approach required for many pain problems, especially those of more chronic duration. A careful evaluation of psychological and social factors contributing to the pain complaint is necessary to prescribe these drugs rationally.

The antidepressants, neuroleptics, and benzodiazepines are often used for the initial control of target symptoms such as depression, anxiety, abnormal muscle tension, insomnia and fatigue. TCAD and occasionally neuroleptics are also used for withdrawal/detoxication from narcotics, other analgesics, minor tranquillizers, and alcohol (Khatami et al 1979, Halpern 1982). Combinations of TCAD and narcotics are used for some pain disorders refractory to either alone.

Rapid tranquillisation

Rapid tranquillisation protocols address the problem of severely disturbed and violent patients who have not responded to non-pharmacological approaches. The risks of administering psychotropic drugs (notably cardiac arrhythmia with high-dose antipsychotics) then greatly outweigh those of non-treatment.

A first step is to offer oral medication, usually haloperidol, olanzapine or risperidone with or without the benzodiazepine, lorazepam. If this is not accepted or fails to achieve control despite repeated doses, the intramuscular route is used to administer a benzodiazepine (e.g. lorazepam or midazolam) or an antipsychotic (e.g. haloperidol or olanzapine), or both (but intramuscular olanzapine should not be given with a benzodiazepine as excess sedation may ensue). After emergency use of an intramuscular antipsychotic or benzodiazepine, pulse, blood pressure, temperature and respiration are monitored, and pulse oximetry (for oxygen saturation) if consciousness is lost.

Zuclopenthixol acetate i.m. was previously used for patients who do not respond to two doses of haloperidol i.m. This usually induces a calming effect within 2 h, persisting for 2–3 days. Clinicians are now becoming reluctant to use this heavily sedating preparation other than for patients who have previously responded well to it, and never use it for neuroleptic-naïve patients. Patients must be observed with care following administration. Some will require a second dose within 1–2 days.

Amobarbital and paraldehyde have a role in emergencies only when antipsychotic and benzodiazepine options have been exhausted.

Psychotropic Medicines

Psychotropic medicines merit special attention both because they play an integral role in traditional religious/medical practices that mediate between the spirit and human worlds and Western observers have misrepresented the meaning and use of psychoactive substances in traditional contexts. Here we concentrate on this second aspect, noting that Westerners have perceived psychotropics as exotic markers of ‘other’ cultures that use these medicines as part of shamanic rituals, while in the West psychotropics have been transported to different social contexts where they became illicit, recreational drugs. Both the exotic and recreational-drug perspectives obscure the traditional meanings associated with psychotropic substances, which are better understood by situating their use within the broader social context in which they occur, and by apprehending the full range of biological actions that psychotropics exhibit.

Western researchers have highlighted the significance of psychoactive properties for achieving altered states of consciousness that are requisite to conduct healing. For example, much has been published about the role in shamanic healing of such psychotropics as ayahuasca, peyote, and datura. These accounts emphasize personalistic elements of diagnosis and healing. While psychotropics do play an important role in magicoreligious healing, this is not the only therapeutic context in which they are important. The bioscientific focus on psychoactivity overlooks the potential for physiologic (nonpsychotropic) effects.

An interesting example is ayahuasca, an infusion of the Banisteriopsis vine and other plants whose combined β-carbolines and indole alkaloids produce the hallucinogenic effects that Amazonian shamans employ in healing rituals. However, the actions of ayahuasca extend beyond psychoactivity. For example, it is antiparasitic, due both to the action of β-carbolines and to the strongly emetic and purgative (worm-expelling) action of the infusion. This antiparasitic action is important for populations who use ayahuasca, as the lowland tropics are home to many intestinal and other parasites. To deflect some of the attention on psychoactivity, it could be argued that the nature and intensity of the psychotropic visions, which the healers manipulate by admixing plants, may be indicators that the healers use to determine the therapeutic effectiveness and dose of ayahuasca for a variety of disorders. From this perspective, ayahuasca could also be understood as the delivery medium for a long list of admixture plant medicines, which is facilitated in part through the inhibition of monoamine oxidase by β-carbolines. In other words, in some traditional therapies, antiparasitic and other actions are the primary objective, and psychoactivity is used primarily as a dose marker.

6.06.2 Classification of Drugs Used in Psychiatry

Psychotropic drugs are those whose main clinical effect is to produce a change in the psychological state. Psychotropic drugs used in psychiatry are conventionally divided into different classes, but the therapeutic actions of particular compounds are not confined to one diagnostic category. For example, SSRIs are classified as antidepressants and are effective in the treatment of major depression, but they also produce useful therapeutic effects in panic disorder, obsessive compulsive disorder and social phobia (Cowen, 1997). This breadth of effect does not mean that the latter syndromes are forms of depression. It merely emphasizes that the neuropsychological consequences of facilitating brain serotonin function may provide beneficial effects in a variety of psychiatric disorders.

Although there is considerable understanding of the pharmacological actions of psychotropic drugs, little is known about the neuropsychological consequences of these pharmacological actions and about the ways in which neuropsychological changes are translated into clinical benefit in different diagnostic syndromes. At present, therefore, the best plan is to classify drugs according to their major therapeutic use but to bear in mind therapeutic effects of different classes of drugs may overlap (Table 3).

Table 3. Classification of clinical psychotropic drugs.

These groups of drugs will be discussed in turn. Subsequently, general advice will be given about the use of psychotropic drugs in different psychiatric disorders and how they may be combined with psychological methods of treatment.

Elimination

Psychotropic drugs are generally eliminated from the body by renal excretion of water soluble metabolites. The rate of elimination of a drug is usually proportional to its plasma concentration, a phenomenon referred to as first-order elimination kinetics. Some drugs (e.g. alcohol when its plasma concentration reaches 10 mg/100 mL) are subject to zero-order elimination kinetics in which elimination mechanisms become saturated and elimination proceeds thereafter at a constant rate and is not proportional to the drug's plasma concentration.

Despite the fact that psychotropic drugs are largely eliminated by renal excretion, there is no general restriction on the use of such drugs in patients with mild to moderate renal impairment. However, the dose of amisulpride should be reduced and chloral hydrate, lithium and acamprosate should be avoided in patients with moderate renal impairment, while clozapine is contraindicated in severe renal impairment.

Psychotropic Drugs

Psychotropic drugs have long been used for mental disorder treatments in children. While nondrug therapies are available (e.g., behavioral therapy) and generally perceived as less invasive, drug intervention may be necessary depending on the severity of illness and other risk factors associated with each patient. Over the last few decades, the rate of psychotropic medication prescriptions for children has rapidly increased across countries, particularly in the United States (Steinhausen, 2015). More specifically, in the year 2000, the prevalence of all-class psychotropic medication prescriptions in youth was 2.9% in Netherlands and 2.0% in Germany, while it was 6.7% in the United States (Zito et al., 2008). This trend is accompanied by a growing concern that children may be overprescribed with psychotropic medications, especially for the conditions such as ADHD (Sohn et al., 2016; Zito et al., 2008). The elevated acceptance of pharmacotherapy in treating childhood mental disorder is in part contributed to successful discoveries of psychotropic drugs for pediatric use (Domino et al., 2008; Sohn et al., 2016). Also, it was argued that cost containment strategies exercised by managed care have led to the increased demand for psychotropic drugs over alternative therapies (Domino, 2012; Rapoport, 2013). More specifically, to reduce health-care costs, expensive psychiatric care is primarily allocated to medication clinics, and nondrug therapies are provided mainly by nonphysicians including psychologists, social workers, and counselors. As Rapaport speculated, “(I)t is probable, that the increase in medication use results in part from the desire of physicians to be helpful with what they have at hand given their lack of flexibility with respect alternate treatment delivery” (Rapoport, 2013).

Among psychotropic medications that are available for pediatric use, antipsychotics have been subject to a major criticism. Antipsychotic medications are used for the treatment of mental disorders including psychosis, schizophrenia, and bipolar disorder. These medications can be broadly categorized into two classes: (1) first-generation antipsychotics that were discovered in the 1950s and (2) second-generation antipsychotics that were introduced during 1990s. Second-generation antipsychotics were marketed as a safer agent as they showed reducing adverse side effects that were common in the first-generation agents, such as extrapyramidal symptoms. This resulted in the prevalent use of second-generation antipsychotics not only for the licensed indications (e.g., schizophrenia, psychoses) but also for off-label conditions and symptoms (e.g., ADHD). However, several postmarketing clinical trials and pharmacoepidemiological studies evaluated the risk of second-generation antipsychotics and reported that children taking these drugs are at a greater risk of weight gain (Sporn et al., 2007), cardiometabolic syndrome (Correll et al., 2009), and type 2 diabetes (Sohn et al. 2015).

Antidepressant treatment in children has also been extensively discussed. While double-blind clinical trials have shown that SSRIs could be successfully used in children to treat depression (Pine, 2002), the extent of knowledge and understanding about antidepressant treatment in children is still limited compared to what is known in adults. Great variations in the effect size (Hetrick et al., 2007) and the confirmed risk of suicidality (Hammad et al., 2006) raise a concern whether the benefits of antidepressant treatment would outweigh the risks to children.

Mechanism of action

Psychoactive drugs are thought to exert their effect through actions on the neurotransmitters in the central nervous system (CNS). Thus far, over 100 neurotransmitters have been identified. The most important ones include gamma amino butyric acid (GABA), acetylcholine (Ach) and the biogenic amines (monoamines), of which the last can be further subdivided into tryptophan-derived indoleamines (serotonin and melatonin) and tyrosine-derived catecholamines (dopamine, norepinephrine, and epinephrine) (Table 5-5). Following the depolarization of the presynaptic cell membrane, neurotransmitters are released into the synaptic cleft. These released neurotransmitters then bind to the receptors, which results in the transduction of the signal to the postsynaptic membrane. Signal transduction ceases again upon deactivation of the activity of the neurotransmitters. This may occur through enzymatic degradation, reuptake in the presynaptic cell via membrane channels, and activation of the autoreceptors (located on the presynaptic membrane) that block the continued release of the neurotransmitters.

Depending on the type of receptor involved, the release of the neurotransmitters may exert excitatory or inhibitory effects. With continued stimulation of the postsynaptic receptors by the neurotransmitters or psychoactive drugs (agonists), downregulation or hyposensitization of the receptors may occur. This downregulation is one of the proposed mechanisms of action of the so-called reuptake inhibitors, which prolong the effect of the neurotransmitters by blocking their reuptake. Alternatively, the receptors that are not stimulated by the neurotransmitters or are blocked by the drugs (antagonists) can become up-regulated or hypersensitive. Alterations in neurotransmitter concentrations and receptor activities result in physiologic and behavioral changes. The effects depend on the type of psychoactive drugs and neurotransmitters involved.

9.01.6.2 Psychopharmacology

Psychotropic medication is any medication prescribed to stabilize or improve mood, mental status, or behavior (Kalachnik et al., 1995). It is used as one part of a comprehensive treatment plan to address an individual's psychiatric symptoms or aberrant behavior. Ideally, the medication acts as a setting event for the occurrence of appropriate behavior when maladaptive behavior is reduced. Thus, psychotropic medication can allow the individual to function more fully or appropriately at school, work, or home. Psychotropic medication should be used to enhance the individual's quality of life rather than to strictly reduce aberrant or undesirable behavior (Ellis, Singh, & Singh, 1997).

Kalachnik et al. (1995), as part of the International Consensus Conference on Psychopharmacology, delineated guidelines for the use of psychotropic medication with persons with mental retardation and other developmental disabilities (see Table 2). The following sources were utilized in the formation of the guidelines: (i) regulatory (e.g., Health Care Financing Administration, 1992); (ii) accreditation (e.g., Joint Commission on Accreditation of Healthcare Organizations, 1995); (iii) professional (e.g., American Psychiatric Association Committee on Research on Psychiatric Treatments, 1992); (iv) litigation (e.g., Wyatt v. Stickney, 1972); (v) legislation (e.g., Civil Rights of Institutionalized Persons Act, 1981); and (vi) proclamations and declarations (e.g., Assembly of the United Nations, “Declaration on the Rights of Mentally Retarded Persons”; see Beyer, 1988; Kalachnik et al., 1995; Singh et al., 1992). The guidelines are endorsed by professionals in the field of mental retardation and serve as a model for appropriate use.

Table 2. Guidelines for the use of psychotropic medication.

1.

Psychotropic medication definition. A psychotropic medication is any drug prescribed to stabilize or improve mood, mental status, or behavior.

Inappropriate use. Psychotropic medication shall not be used excessively, as punishment, for staff convenience, as a substitute for meaningful psychosocial services, or in quantities that interfere with an individual's quality of life.

Multidisciplinary care plan. Psychotropic medication must be used within a coordinated multidisciplinary care plan designed to improve the individual's quality of life.

Diagnostic and functional assessment. The use of psychotropic medication must be based upon a psychiatric diagnosis or a specific behavioral-pharmacological hypothesis resulting from a full diagnostic and functional assessment.

Informed consent. Written informed consent must be obtained from the individual, if competent, or the individual's guardian before the use of any psychotropic medication and must be periodically renewed.

Index behaviors and empirical measurement. Specific index behaviors and quality of life outcomes must be objectively defined, quantified, and tracked using recognized empirical measurement methods in order to monitor psychotropic medication efficacy.

Side effects monitoring. The individual must be monitored for side effects on a regular and systematic basis using an accepted methodology which includes a standardized assessment instrument.

Tardive dyskinesia monitoring. If antipsychotic medication or other dopamine blocking drugs (e.g., amoxapine or metoclopramide) are prescribed, the individual must be monitored for tardive dyskinesia on a regular and systematic basis using a standardized assessment instrument.

Regular and systematic review. Psychotropic medication must be reviewed on a regular and systematic basis. Clinical reviews must be conducted on a regular and systematic basis by the prescriber. Data reviews must be conducted on a regular and systematic basis by appropriate members of the multidisciplinary team.

Lowest “optimal effective dose.” Psychotropic medication must be reviewed on a periodic and systematic basis to determine if it is still necessary or, if it is, if the lowest “optimal effective dose” is prescribed.

Frequent changes. Frequent drug and dose changes should be avoided.

Poly pharmacy. Keep psychotropic medication regimens as simple as possible in order to enhance compliance and minimize side effects.

Practices to minimize. Minimize the following practices to the degree possible: (i) long-term use of PRN (as needed) orders; (ii) long-term use of benzodiazepine antianxiety medications such as diazepam; (iii) use of long-acting sedative-hypnotic medications such as chloral hydrate; (iv) long-term use of shorter-acting sedative-hypnotics such as temazepam (Restoril); (v) anticholinergic use such as benztropine without signs of EPSE; (vi) long-term anticholinergic use; (vii) antipsychotic medication at high doses; (viii) use of phenytoin, phenobarbital, and primidone as psychotropic medication.

Peer or external review. Establish a system of peer or external review of psychotropic medication prescribing which incorporates a system of flagging up cases of greatest concern.

Source: Bisconer, Sine, and Zhang (1996).

Administration and monitoring of psycho-tropic medication should be conducted by a psychiatrist in cooperation with all individuals who interact with the client on a day-to-day basis (e.g., psychologist, teachers, caretakers). A multidisciplinary team approach enhances the reliable assessment as to whether the medication is successfully addressing the behaviors or psychiatric symptoms it was prescribed to address, and whether the medication is causing undesirable side effects (e.g., sedation, agitation) that interfere with the client's day-to-day activity. Medication monitoring processes are enhanced by the ongoing collection of systematic data that reflect the frequency, duration, and intensity of target behavior or psychiatric symptoms. This type of data is best collected by individuals who interact with the client for extended periods of time each day or night. These individuals can be trained to reliably assess and record the frequency, duration, and intensity of occurrence of aberrant behavior or psychiatric symptoms.

A thorough psychotropic medication review should take place every 3–6 months unless more frequent reviews are indicated (e.g., change in medication or dose, increase in behavior or psychiatric symptoms). The process should include a review of the client's psychiatric/ behavioral history; a careful evaluation of the client's medical diagnoses and current medical status; behavioral changes since the last review (frequency, duration, intensity); observed medication side effects; a report of any environmental changes that may impact the client's behavior or psychiatric symptoms; a progress report on skills training designed to decrease targeted behavior; and any changes to long-term plans for treatment and education (Bisconer, Zhang, & Sine, 1995).

Medication side effects should be systematically monitored by the psychiatrist via appropriate laboratory tests and objective screening procedures (see Gadow & Poling, 1988 for a review of screening instruments). The psychiatrist can rely on trained care staff and other professionals to conduct periodic screenings for side effects. These results can then be reviewed and validated when the psychiatrist meets with the client.

Table 3 provides psychotropic and antiepileptic medications by class, generic name, and recommended dosage by age for persons with mental retardation. Table 4 provides the most common indications and side effects for different classes of medications. A comprehensive review of psychotropic medication use with persons with mental retardation can be found in the following sources (Aman & Singh, 1991; Ellis et al., 1996; Singh, Ellis, & Singh, 1994).

Table 3. Recommended doses for the various classes of psychotropic drugs.

Source: Ellis et al. (1996); reprinted with permission from the authors.

Table 4. Psychiatric and behavioral indications and side effects of various classes of drugs.

Source: Ellis et al. (1996); reprinted with permission from the authors.

5.18.9 Psychopharmacology

Psychotropic medication should be considered as a possible treatment modality for all adolescent suicidal behavior. At times, medication is clearly indicated for a particular psychiatric disorder such as major depression or bipolar affective disorder. At other times, medications may be helpful in reducing acute symptomology which, in turn, may improve the adolescent's acceptance and receptivity to other psychotherapies (Berman & Jobes, 1991). Of course, prescribing medications for suicidal adolescents requires careful monitoring, particularly for those adolescents thought to be at higher risk for reattempts. However, there have not been specific drug trials that have examined effects of medication on the functioning of suicide attempters.