Chapter 9 — Pharmacologic Management Pharmacologic Risk Factors
Addiction is not a fixed and rigid event. Like psychiatric disorders, addiction is a dynamic process, with fluctuations in severity, rate of progression, and symptom manifestation and with differences in the speed of onset. Both disorders are greatly influenced by several factors, including genetic susceptibility, environment, and pharmacologic influences. Certain people have a high risk for these disorders (genetic risk); some situations can evoke or help to sustain these disorders (environmental risk); and some drugs are more likely than others to cause psychiatric or AOD use disorder problems (pharmacologic risk).
Pharmacologic effects can be therapeutic or detrimental. Medication often produces both effects. Therapeutic pharmacologic effects include the indicated purposes and desired outcomes of taking prescribed medications, such as a decrease in the frequency and severity of episodes of depression produced by antidepressants.
Detrimental pharmacologic effects include unwanted side effects, such as dry mouth or constipation resulting from antidepressant use. Side effects perceived as noxious by patients may decrease their compliance with taking the medications as directed.
Some detrimental pharmacologic effects relate to abuse and addiction potential. For example, some medications may be stimulating, sedating, or euphorigenic and may promote physical dependence and tolerance. These effects can promote the use of medication for longer periods and at higher doses than prescribed.
Thus, prescribing medication involves striking a balance between therapeutic and detrimental phar-macologic effects. For instance, therapeutic antianxiety effects of the benzodiazepines are balanced against detrimental pharmacologic effects of sedation and physical dependency. Similarly, the desired therapeutic effect of abstinence from alcohol is balanced by the possibility of damage to the liver from prescribed disulfiram (Antabuse).
Side effects of prescription medications vary greatly and include detrimental pharmacologic effects that may promote abuse or addiction. With regard to patients with dual disorders, special attention should be given to detrimental effects, in terms of 1) medication compliance, 2) abuse and addiction potential, 3) AOD use disorder relapse, and 4) psychiatric disorder relapse (Ries, 1993a).
Not all psychiatric medications are psychoactive. The term psychoactive describes the ability of certain medications, drugs, and other substances to cause acute psychomotor effects and a relatively rapid change in mood or thought. Changes in mood include stimulation, sedation, and euphoria. Thought changes can include a disordering of thought such as delusions, hallucinations, and illusions. Behavioral changes can include an acceleration or retardation of motor activity. All drugs of abuse are by definition psychoactive.
In contrast, certain nonpsychoactive medications such as lithium (Eskalith) can, over time, normalize the abnormal mood and behavior of patients with bipolar disorder. Because these effects take several days or weeks to occur, and do not involve acute mood alteration, it is not accurate to describe these drugs as psychoactive, euphorigenic, or mood altering. Rather, they might be described as mood regulators. Similarly, some drugs, such as antipsychotic medications, cause normalization of thinking processes but do not cause acute mood alteration or euphoria.
However, some antidepressant and antipsychotic medications have pharmacologic side effects such as mild sedation or mild stimulation. Indeed, the side effects of these medications can be used clinically. Physicians can use a mildly sedating antidepressant medication for patients with depression and insomnia, or a mildly stimulating antipsychotic medication for patients with psychosis and hypersomnia or lethargy (Davis and Goldman, 1992). While the side effects of these drugs include a mild effect on mood, they are not euphorigenic. Nevertheless, case reports of misuse of nonpsychoactive medications have been noted, and use should be monitored carefully in patients with dual disorders.
While psychoactive drugs are generally considered to have high risk for abuse and addiction, mood- regulating drugs are not. A few other medications exert a mild psychoactive effect without having addiction potential. For example, the older antihistamines such as doxylamine (Unisom) exert mild sedative effects, but not euphoric effects.
Some drugs promote reinforcement, or the increased likelihood of repeated use. Reinforcement can occur by either the removal of negative symptoms or conditions or the amplification of positive symptoms or states. For example, self-medication that delays or prevents an unpleasant event (such as withdrawal) from occurring becomes reinforcing. Thus, using a benzodiazepine to avoid alcohol withdrawal can increase the likelihood of continued use. Positive reinforcement involves strengthening the possibility that a certain behavior will be repeated through reward and satisfaction, as with drug-induced euphoria or drug-induced feelings of well-being. A classic example is the pleasure derived from moderate to high doses of opiates or stimulants. Drugs that are immediately reinforcing are more likely to lead to psychiatric or AOD use problems.
Long-term or chronic use of certain medications can cause tolerance to the subjective and therapeutic effects and prompt dosage increases to recreate the desired effects. In addition, many drugs cause a well-defined withdrawal phenomenon after the cessation of chronic use. Patients’ attempts to avoid withdrawal syndromes often lead them to additional drug use. Thus, drugs that promote tolerance and withdrawal generally have higher risks for abuse and addiction.
As can be seen, there are pharmacologic as well as hereditary and environmental factors that influence the development of AOD use problems. All of these factors should be considered prior to prescribing medication, especially when the patient is at high risk for developing an AOD use disorder. High-risk patients include people with both psychiatric and AOD use disorders, as well as patients with a psychiatric disorder and a family history of AOD use disorders.
One aspect of this issue relates to the pharmacologic profile of certain medications that are used in the treatment of specific psychiatric disorders. For instance, many medications used to treat symptoms of depression and psychosis are not psychoactive or euphorigenic. However, many of the medications used to treat symptoms of anxiety, such as the benzodiazepines, are psychoactive, reinforcing, have potential for tolerance and withdrawal, and have an abuse potential, especially among people who are at high risk for AOD use disorders. Other antianxiety medications, such as buspirone (BuSpar), are not psychoactive or reinforcing and have low abuse potential, even among people at high risk.
Thus, decisions about whether and when to prescribe medication to a high-risk patient should include a risk-benefit analysis that considers the risk of medication abuse, the risk of undertreating a psychiatric problem, the type and severity of the psychiatric problem, the relationship between the psychiatric disorder and the AOD use disorder for the individual patient, and the therapeutic benefits of resolving the psychiatric and AOD problems.
For example, the early and aggressive medication of high-risk patients who have severe presentations of psychotic depression, mania, and schizophrenia is often necessary to prevent further psychiatric deterioration and possible death. For these patients, rapid and aggressive medication can shorten the length of the psychiatric episodes. In contrast, prescribing benzodiazepines to high-risk patients with similarly severe anxiety involves a substantial risk of promoting or exacerbating an AOD use disorder. For these high-risk patients, the use of psychoactive medication should not be the first line of treatment.
Rather, for some high-risk patients, treatment efforts should involve a stepwise treatment model that begins with conservative approaches and progressively becomes more aggressive if the treatment goals are not met (Landry et al., 1991a). For example, the stepwise treatment model for treating high-risk patients with anxiety disorders may involve three progressive levels of treatment: 1) nonpharmacologic approaches when possible; 2) nonpsychoactive medication when nonpharmacologic approaches are insufficient; and 3) psychoactive medications when other treatment approaches provide limited or no relief (Landry et al., 1991).
Pharmacologic Risk Factors
A medication may have:
A Stepwise Management Approach For Mild and Moderate Mental Disorders
*For severe conditions, such as psychotic depression, mania, and schizophrenic disorders, rapid and aggressive use of medications is needed to prevent danger to self or others and further psychiatric deterioration.
Depending upon the psychiatric disorders and personal variables, numerous nonpharmacologic approaches can help patients manage all or some aspects of their psychiatric disorders (Weiss and Billings, 1988). Examples include psychotherapy, cognitive therapy, behavioral therapy, relaxation skills, meditation, biofeedback, acupuncture, hypnotherapy, self-help groups, support groups, exercise, and education.
Some medications are not psychoactive and do not cause acute psychomotor effects or euphoria. Some medications do not cause psychoactive or psychomotor effects at therapeutic doses but may exert limited psychoactive effects at high doses (often not euphoria, but sometimes dysphoria).
For practical purposes, all of these medications can be described as nonpsychoactive, since the psychoactive effect is not prominent. Medications used in psychiatry that are not euphorigenic or significantly psychoactive include but are not limited to the azapirones (for example, buspirone), the amino acids, beta-blockers, antidepressants, monoamine oxidase inhibitors, antipsychotics, lithium, antihistamines, anticonvulsants, and anticholinergic medications.
Some medications can cause significant and acute alterations in psychomotor, emotional, and mental activity at therapeutic doses. At higher doses, and for some patients, some of these medications can also cause euphoric reactions. Medications that are potentially psychoactive include opioids, stimulants, benzodiazepines, barbiturates, and other sedative-hypnotics.
One of the emphases of stepwise treatment is to encourage nondrug treatment strategies for each emerging symptom before medications are prescribed. Nondrug treatment strategies alone are inappropriate for acute and severe symptoms of schizophrenia and mood disorders, but nondrug strategies do have their place in the treatment of virtually any psychiatric problem, and may provide partial or total relief of some symptoms related to severe psychiatric disorders. For example, relaxation therapy can minimize or eliminate somatic symptoms of anxiety that may accompany an agitated depression.
A second emphasis of stepwise treatment is to encourage the use of medications that have a low abuse potential. This conservative approach must be balanced against other therapeutic and safety considerations in acute and severe conditions, such as psychosis or mania. On the other hand, a conservative approach is not the same as undermedication of psychiatric problems. Undermedication often leads to psychiatric deterioration and may promote AOD relapse. There should be a balance between effective treatment and safety.
A third emphasis of stepwise treatment is to encourage the idea that different treatment approaches should be viewed as complementary, not competitive. For example, if psychotherapy or group therapy does not provide complete relief from a situational depression (such as prolonged grief), then antidepressants should be considered as an adjunct to the psychotherapy, but not as a substitute for psychotherapy.
In practice, treatment providers often use a combination of drug and nondrug strategies. This practice includes medication to treat the acute manifestations of the disorder while the individual learns long-term management strategies. For example, an individual may be prescribed nonpsychoactive buspirone to reduce anxiety symptoms while learning stress reduction techniques and attending group therapy.
These guidelines are broad, general, and more applicable to chronic than to acute psychiatric problems. Also, these guidelines have limited application to very severe psychiatric problems.
Several antihistamines are approved for sale as over-the-counter hypnotics, including diphenhydramine (Nytol, Benadryl), doxylamine (Unisom), and pyrilamine (Quiet World). The efficacy of these drugs is not uniform, and tolerance to the anxiolytic and hypnotic effects is rapid, limiting their utility for episodic use. Antihistamines are frequently prescribed for mild anxiety and insomnia, particularly for patients in general hospitals, patients with physical illness (Salzman, 1989), and elderly patients.
In general, the early antihistamines exert very mild anxiolytic and hypnotic effects, but lack euphoric properties and do not promote physical dependence (Meltzer, 1990). While lacking significant abuse potential themselves, antihistamines may cause problems for some patients by reinforcing the idea of self-medication of insomnia and anxiety. Taken in high doses, antihistamines may cause acute delirium, alter mood (often causing dysphoria), or cause morning-after depression. Under close medical supervision, the conservative use of antihistamines can be valuable in treating brief episodes of insomnia during an otherwise drug-free recovery process. Patients in recovery should be discouraged from purchasing and using over-the-counter antihistamines.
The antidepressants include several types of medication, such as tricyclics, monoamine oxidase inhibitors (MAOIs), and other, newer, antidepressants such as trazodone (Desyrel), bupropion (Wellbutrin), sertraline (Zoloft), and fluoxetine (Prozac). Antidepressants are effective for the treatment of depression, and several are valuable for the treatment of anxiety disorders, including generalized anxiety disorder, phobias, and panic disorder.
The antidepressants are not euphorigenic, and do not cause acute mood alterations. Rather, they are mood regulators and diminish the severity and frequency of depressive episodes; they also have anti-panic capabilities unrelated to sedation.
While the general effects of most of the older tricyclic antidepressants are similar, they differ considerably with regard to side effects. For example, some antidepressants such as doxepin (Sinequan) exert a mild sedating effect, while others such as protriptyline (Vivactil) exert a mild stimulating effect. These side effects can be clinically useful. For example, clinicians might give antidepressants with slight sedating effects to depressed patients with insomnia or give those with mild stimulating effects to depressed patients who experience low energy and hypersomnia (Davis and Goldman, 1992).
Other side effects of tricyclic antidepressants are common. Anticholinergic effects such as dry mouth, blurred vision, constipation, urinary hesitancy, and toxic-confusional states are common anticholinergic effects. Adrenergic activation symptoms may include tremor, excitement, palpitation, orthostatic hypotension, and weight gain. These noxious side effects are frequently the cause of requests to switch from one medication type to another. Also, side effects often prompt discontinuation of medication, which may provoke reemergence of the psychopathology. Tricyclics unfortunately are quite toxic when combined with AODs. Therefore use of tricyclic antidepressants in early recovery should be carefully monitored.
More expensive, but much less toxic when used with AODs, are the newer serotonin reuptake inhibitors including fluoxetine, paroxitine (Paxil), and sertraline. These agents also have anticompulsive effects, and their side effects tend to be slight to moderate stimulation rather than sedation. They are much safer to use in early recovery.
Overall, the use of antidepressants is consistent with a psychoactive-drug-free philosophy, does not compromise recovery from addiction, and enhances recovery from depressive and panic disorders. However, patient information must include clear explanations of the reasons for prescribing, the expected results, and the risks of adverse effects, including overdose. The risk-benefit analysis must include the risk of lethal overdose with tricyclic antidepressants, especially for depressed patients (Reid, 1989).
The beta-blockers such as propranolol (Inderal) are well-recognized medications for the treatment of hypertension, cardiac arrhythmias, and angina pectoris. They also have clinical efficacy as an adjunct in the treatment of anxiety (Lader, 1988). The b-blockers may reduce or eliminate the adrenergic discharge associated with panic attacks, thus blocking the somatic components of some anxiety states, especially when somatic symptoms predominate (Trevor and Way, 1989). b-blockers diminish the tremor and restlessness related to lithium or antipsychotics in some patients.
The Beta-blockers are not psychoactive, euphorigenic, or mood altering. Since tolerance to the anti-panic effects of b-blockers develops rapidly, they cannot be used for extended periods of time for this purpose. Rather, they are often used prophylactically for anticipated panic-producing situations, or for episodes of anxiety that may last a few days. The b-blockers are also used to decrease acute and subacute anxiety symptoms during detoxification from sedative-hypnotics such as the benzodiazepines. Overall, the use of b-blockers is consistent with a psychoactive-drug-free philosophy, does not compromise recovery from addiction, and can be an important adjunct to anxiety management.
While all of the benzodiazepines have anxiolytic characteristics, they differ in their effectiveness in treating generalized anxiety disorder, mixed anxiety and depression, panic attacks, phobic-avoidance behaviors, and insomnia. In general, the benzodiazepines promote sedation, central nervous system depression, and muscle relaxation, and thus are effective for anxiety reduction and, at higher doses, for short-term management of insomnia.
The benzodiazepines are psychoactive, mood altering, and reinforcing. Chronic use and subsequent cessation can cause withdrawal symptoms. Studies have shown that the benzodiazepines are not uniformly euphorigenic. Also, patients with a family and personal history of AOD abuse and addiction are more likely to experience euphoria with the benzodiazepines (Ciraulo et al., 1988, 1989).
Benzodiazepines are the most commonly used agents to moderate alcohol withdrawal and prevent dangerous withdrawal conditions such as delirium tremens and seizures. They are also widely used during detoxification from sedative-hypnotics. The benzodiazepines are frequently prescribed for use alone and in combination with antipsychotics during the treatment of acute psychotic symptoms caused by mania, schizophrenia, and drugs of abuse such as cocaine. Such treatment should be limited to the acute episode for most patients with dual disorders, so that one problem (psychosis) is not replaced by another problem (physical dependence or addiction). The benzodiazepines are not usually recommended for long-term use in patients with dual disorders unless all nonpsychoactive approaches have failed. That is, if all other less potentially adverse medications have proven inadequate and the benzodiazepines are indicated, then careful dispensing, regulation of dose, and scrupulous monitoring are required.
Overall, the use of benzodiazepines after the medical management of withdrawal is not consistent with a psychoactive-drug-free philosophy and may compromise recovery from addiction (Zweben and Smith, 1989). However, they can be used in the management of acute and severe withdrawal, panic, and psychosis with special guidelines in nonroutine situations.
Buspirone is the most well known of a new group of drugs (the azapirones) that selectively diminish multiple symptoms of anxiety without the acute mood alteration, sedation, or associated somatic side effects seen in the sedative-hypnotic anxiolytics. Buspirone is useful for generalized anxiety disorder, chronic anxiety symptoms, anxiety with depressive features, and anxiety among elderly patients. Buspirone is generally equivalent to the benzodiazepines with regard to anxiety management (Petracca et al., 1990; Strand et al., 1990). However, it takes several weeks for the maximal therapeutic effect of buspirone to occur.
Buspirone is not psychoactive, mood altering, or euphorigenic (Balster, 1990). In particular, buspirone does not cause the mood alteration, central nervous system depression, sedation, and muscle relaxation associated with the benzodiazepines. However, many people with experience taking benzodiazepines may associate these mood alterations with relief of anxiety. As a result, patients who have experience with the benzodiazepines may misinterpret the absence of these side effects as evidence that the medication is ineffective. Educating patients about the distinction between anxiety reduction and sedation and about treatment expectations can avoid these misinterpretations.
Overall, the use of buspirone is consistent with a psychoactive-drug-free philosophy, does not compromise recovery from addiction, and enhances recovery from anxiety disorders.
Used in the form of a patch (Catapres Transdermal Therapeutic System patches) or tablets (Catapres), clonidine is well recognized as a treatment for symptoms of hypertension, including hypertensive symptoms that occur during withdrawal from depressant drugs, especially the opioids. In addition, clonidine appears to have anxiolytic and anti-panic properties comparable to the antidepressant imipramine. Patients may become less anxious but remain symptomatic. Some patients who have anxiety-depression or panic-anxiety experience significant antianxiety effects from clonidine. The anti-panic effect is the result of clonidine’s ability to decrease locus ceruleus firing and thus decrease adrenergic discharge. Thus, clonidine may be useful for short-term use in the treatment of refractory anxiety with panic (Domisse and Hayes, 1987; Uhde et al., 1989).
Clonidine is not psychoactive, euphorigenic, or mood altering. Clonidine may have significant antianxiety effects when administered to patients with anxiety-depression and panic-anxiety. However, tolerance to the anti-panic effects of clonidine can develop within several weeks. Thus, clonidine may be most useful for short-term use in the treatment of refractory panic disorder.
Overall, the use of clonidine is consistent with a psychoactive-drug-free philosophy, does not compromise recovery from addiction, and may be an adjunct in the treatment of anxiety symptoms.
The neuroleptic medications are most effective in suppressing the positive symptoms of psychosis such as hallucinations, delusions, and incoherence. In addition, they may help reduce disturbances of arousal, affect, psychomotor activity, thought content, and social adjustment (Africa and Schwartz, 1992).These psychotic symptoms may accompany schizophrenia, brief reactive psychosis, schizophreniform disorder, mania, depression, and organic mental disorders induced by AODs and medical conditions (Ries, 1993a).
Although neuroleptic medications are equally effective in suppressing psychotic symptoms, individuals may respond to one medication better than another. The chief differences among the neuroleptics relate to dosage, onset of effects, and (especially) side effects. Some side effects may be clinically useful, such as nighttime sedation with chlorpromazine or avoidance of appetite stimulation with molindone (Moban) (Africa and Schwartz, 1992).
In general, low-potency neuroleptics, for example, chlorpromazine, thioridazine (Mellaril), and clozapine (Clozaril), have significant sedative and hypotensive properties. Tolerance to these properties may develop within a few weeks. Also, low-potency neuroleptics are inherently anticholinergic, so that the use of additional anticholinergic drugs to prevent extrapyramidal symptoms may be unnecessary. The high-potency neuroleptics such as fluphenazine (Prolixin) and haloperidol (Haldol) cause more extrapyramidal side effects than the low-potency medications.
The extrapyramidal system is a network of nerve pathways that links nerves in the surface of the cerebrum (the deep mass of the brain), the basal ganglia deep within the brain, and parts of the brain stem. The extrapyramidal system influences and modifies electrical impulses that are sent from the brain to the skeletal muscles.
When this system is damaged or disturbed, execution of voluntary movements and muscle tone can be disrupted, and involuntary movements, such as tremors, jerks, or writhing movements, can appear. These disturbances are called extrapyramidal syndromes, which can be caused by all of the neuroleptic medications except clozapine.
Extrapyramidal symptoms are unwanted, noxious, and uncomfortable. Compliance with neuroleptic medications is worsened because of the onset of these drug-induced symptoms. A class of medications called anticholinergic agents can eliminate the muscle spasms in the neck, oral, facial, cheek, and tongue regions. Several other types of medications may also be helpful, including amantadine and beta-blockers.
Anticholinergic agents can also reduce the extrapyramidal movement disorder called akathisia, which consists of purposeless movements, usually of the lower extremities, often accompanied by the experience of severe, uncomfortable restlessness. These medications include benztropine (Cogentin), biperiden (Akineton), diphenhydramine (Benadryl), trihexyphenidyl (Antitrem), and procyclidine (Kemadrin). Patient response should be monitored because some anticholinergic medications may be mildly psychoactive for some AOD patients.
Neuroleptic drugs are not euphorigenic and do not cause acute mood or psychomotor alterations. However, side effects are common. Most of the neuroleptics cause sedation as a side effect, although adaptation to the sedative (but not the antipsychotic) effects develops within days or weeks. The anticholinergic side effects of neuroleptic medications can include dry mouth, constipation, and blurred vision. The neuroleptics can also cause extrapyramidal symptoms. The adverse side effects of neuroleptic medications are a frequent cause of medication compliance problems. These adverse effects can also prompt patients to use AODs to self-medicate noxious symptoms.
Because patients with psychotic symptoms often experience significant biopsychosocial problems, the neuroleptics allow them to engage in problem-solving and recovery-oriented interpersonal activities. Overall, the use of neuroleptics is consistent with a psychoactive-drug-free philosophy, does not compromise recovery from addiction, and enhances recovery from psychotic disorders.
Lithium is the standard and first-line treatment for manic episodes, even though 10-14 days may be required before full effect is achieved. The initial symptoms managed by lithium include increased psychomotor activity, pressured speech, and insomnia. Later, lithium diminishes the symptoms of expansive mood, grandiosity, and intrusiveness. Lithium also treats signs related to disorganization of the form of thought such as flight of ideas and loosening of association.
Lithium does not cause acute mood alteration, and is not psychoactive or mood altering. Rather, lithium is a mood regulator, and diminishes symptoms of acute mania. The common adverse effects of lithium include thirst, urinary frequency, tremor, and gastrointestinal distress. Lithium allows patients who may have seriously disabling symptoms to engage in problem-solving and recovery-oriented interpersonal activities. Overall, the use of lithium is consistent with a psychoactive-drug-free philosophy, does not compromise recovery from addiction, and enhances recovery from bipolar disorders.
Anticonvulsants have a role in the management of bipolar disorders, mania, schizoaffective disorder, and alcohol and benzodiazepine withdrawal. In addition, these medications may be prescribed for “flashbacks” related to drug use or post-traumatic stress disorder. These medications, such as carbamazepine (Tegretol) and valproic acid, are not psychoactive. The typically minor side effects of sedation and nausea may emerge as treatment is initiated. Rarely, carbamazepine causes a decrease in white blood cell count. Both medications are monitored according to blood levels. For the treatment of bipolar disorder, the anticonvulsants are most often used when lithium has failed. However, they are occasionally used by highly skilled physicians as first-line treatment. These medications are consistent with a psychoactive-drug-free philosophy, and may enhance the abilities of those who need them to participate in the recovery process.
There are certain risks associated with AOD use and withdrawal among patients who are also being administered medications to treat psychiatric disorders. Because of these risks, serious consideration should be given to inpatient treatment for withdrawal.