CHAPTER-9

PSYCHOPHARMACOLOGY OF REWARD AND DRUGS OF ABUSE

Medication Discontinuation

It is generally best to taper off a medication slowly, usually over several weeks or months, depending on
the medication and the length of time a person has been taking it. With some medications the
consequences of stopping abruptly can be very problematic, but with others they can be serious, even
life threatening. When any psychotropic medication is discontinued, clinicians should be particularly
watchful for changes or worsening of mental status. It is important to note that discontinuation
symptoms are sometimes experienced during dosage reductions or when changing from a longer to a
shorter half-life form of the medication. Also, with certain classes of medications, after discontinuation
of a medication a patient may become unresponsive to that medication. For example, a person who is
stable on lithium for treatment of bipolar disorder and develops a manic episode following
discontinuation of lithium may not respond to lithium when it is restarted. This has also been reported
anecdotally with antidepressants and antipsychotics, though the evidence is not conclusive. It is thought
that each episode, whether it is mania, depression, or psychosis, has a neuro-physiological effect on the
brain (i.e., damage to brain structures and nerve cells) that may make it unresponsive to a medication
that was previously effective. While the discussion is beyond the scope of this book, special precautions
may be necessary for monitoring and managing discontinuation or withdrawal symptoms in newborns if
the mother was on chronic therapy with certain psychotropic medications, such as psycho-stimulants or
benzodiazepines.

Antidepressants

While antidepressants are not considered habit forming, or addictive, abrupt discontinuation can cause
significant symptoms. Certain discontinuation symptoms may occur with all antidepressants, while
others are specific to a given class of antidepressant. There is a potential for relapse into depression or,
paradoxically, mania when an antidepressant is withdrawn too quickly. This can usually be avoided by
tapering the antidepressant slowly, e.g., 25 to 50 percent of the current dose per month. For example, if a
person is taking 40 mg of citalopram (Celexa) daily, it can be tapered by taking 30 mg per day for one
month, then 20 mg per day for a month, then 10 mg per day for a month, and then stopped. Or, if the
person is taking 20 mg per day, it would be reduced to 10 mg daily for one month and then stopped. The
more slowly it is tapered, the less the likelihood of relapse and/or withdrawal symptoms.
Discontinuation symptoms vary by antidepressant class as follows:
 Heterocyclic antidepressants: Dizziness, nausea, vomiting, headache, malaise, sleep
disturbances, increased body temperature, or irritability.
 SSRIs and SNRIs: Agitation, anxiety, tremulousness, dizziness, tinnitus, dysphoria, headache,
insomnia, nightmares, irritability, lethargy, gastrointestinal disturbances, or sensory sensations
described as “electric shocks.” Discontinuation symptoms tend to be more severe with shorter
half-life agents, such as venlafaxine and paroxetine.
 MAOIs: Irritability, pressured or slurred speech, muscle rigidity, increased body temperature,
insomnia, nightmares, muscle spasms, painful muscle contractions, ataxia, electric shock
sensations, or hallucinations. Again, discontinuation symptoms can usually be avoided by
tapering slowly, as shown previously. These symptoms may persist for two or three weeks after
the medication is stopped. One strategy for managing persistent symptoms is to have the patient
take a single dose every few days when the symptoms recur.

Psycho-Stimulants

When discontinuing psycho-stimulants after long-term use, clinicians should monitor for signs of
unmasked depression, dysphoria, sleep disturbances, difficulty concentrating, fatigue, and irritability.
These symptoms usually resolve within a week, with the exception of unmasked depression, which may
require treatment in some cases. Generally, psycho-stimulants can be tapered over several weeks to a
month, depending on the medication, dosage form, and half-life. Concerns about dependence or
addiction with psycho-stimulants are greater for patients with a history of alcohol or drug dependence.

Hypnotics

Benzodiazepine and non-benzodiazepine hypnotics have the potential to be habit forming and produce
tolerance and dependence. Hypnotics can best be tapered by skipping days, e.g., going from daily dosing
to every other night, then every third night, and then as needed or once a week. Discontinuation
symptoms include dysphoria and rebound insomnia. Withdrawal symptoms can include abdominal
cramps, vomiting, sweating, muscle pain, tremors, and seizures. The withdrawal symptoms from having
developed a dependence on the medication will resolve in about two weeks. Even after withdrawal
symptoms have resolved, insomnia or rebound insomnia may persist.

Mood Stabilizers

Mood stabilizers should be tapered slowly, similarly to antidepressants. Abrupt discontinuation of any
type of mood stabilizer can precipitate a manic episode and/or cause mood instability. Other
discontinuation reactions for each type of mood stabilizer are summarized below:
 Lithium: Discontinuation may precipitate a manic episode or other mood instability.
 Anticonvulsant mood stabilizers: Abrupt discontinuation can cause a seizure. Other potential
discontinuation symptoms include headache, dizziness, and shakiness.
 Second-generation antipsychotics: Discontinuation may lead to a manic episode or mood
instability.
 Also, sometimes withdrawal dyskinesias will appear, involving involuntary movements of the
hands, limbs, or face, but they usually resolve within a few weeks to a few months. It is usually
safe to reduce the dose at intervals of one to two weeks, as long as the mood disorder is still
being treated. That is, slow tapering of a mood stabilizer is not likely to cause discontinuation
symptoms, but taking a person with bipolar disorder off all medications is likely to lead to the
reemergence of symptoms of bipolar disorder.

Anti-anxiety Medications (Benzodiazepines)

Benzodiazepine anti-anxiety medications are the most difficult to discontinue, because abrupt
discontinuation can cause severe withdrawal symptoms, including seizures. Also, a rapid dosage
reduction can lead to severe anxiety and/or panic attacks. Therefore, these medications need to be
reduced very gradually. One tapering regimen is to decrease the dose by about 10 percent per week,
recognizing that the last step, reducing to zero, can be very difficult and often takes longer than a week.
So, for example, a current daily dose of 6 mg of alprazolam would be decreased by 0.5 mg each week.
This is usually best done by first switching to the long-acting form, or clonazepam, in order to avoid
peaks and valleys of blood level, which can worsen withdrawal symptoms.

Antipsychotics

Antipsychotics are not associated with significant discontinuation or withdrawal symptoms. However,
abruptly stopping antipsychotics can cause physical symptoms of gastrointestinal problems, dizziness,
headache, or insomnia. Of greatest concern when reducing or discontinuing antipsychotics is the
recurrence of psychotic symptoms. Therefore, dosage reductions must be done slowly and carefully,
with incremental dose reductions at one- to six-month intervals. Unfortunately, sometimes abrupt
discontinuation is necessary, such as when clozapine causes a dangerous drop in the white blood cell
count. In this situation, the risk of psychosis can be reduced by using a different antipsychotic. Previous
chapters have discussed the diagnostic phase of treatment, in which the clinician makes initial decisions
regarding possible referral for medication treatment. We have also outlined basic treatment strategies
and medication doses. The nonmedical therapist is crucially involved in monitoring patient response to
medications: noting signs of symptomatic improvement, the emergence of adverse effects, and, at times,
exacerbation of symptoms. Knowing what to look for and when to direct the patient back to the
prescribing physician is an important task. In this chapter, we will address six important conditions or
circumstances in which a re-referral is indicated: failure to respond, need for dosage adjustment,
unexplained relapse, the onset of new medical conditions, side-effect problems, and discontinuation of
medication treatment.

Failure to Respond

As noted in earlier chapters, a positive medication response is rarely immediate. Most psychotropic
medications require a number of days or weeks to reach adequate blood levels and produce physiologic
changes that yield symptomatic improvement. Also, there exists tremendous variability from patient to
patient regarding absorption and metabolism of medications, which affects the ultimate response time.
Initial doses often must be raised gradually, as tolerance for side effects is achieved and blood levels of
the medication approach therapeutic levels. Critical to appropriate treatment is conducting an adequate
trial. Adequate trials must assume that the correct diagnosis has been made and the patient has actually
taken the medication as prescribed. Beyond this, the two most important variables to consider are dosage
and length of treatment. A general rule with all psychotropics is to use the lowest dose that is effective,
although at the same time not to undertreat. The clinician must be willing to increase doses in order to
achieve meaningful results, while continuously monitoring for the emergence of side effects. Generally,
if patients have been treated with moderate to high doses of psychotropic medications (or at adequate
blood levels) for four or five weeks without noticeable improvement, a re-referral should be made for
dosage increase, augmentation, or perhaps a change to another class of medication. It is not unusual to
encounter patients who have been treated for months (or even years!) on a particular drug or dose
without symptomatic improvement. This is not appropriate. Any condition that warrants medication
treatment is undoubtedly causing considerable suffering. There is no justifiable reason to mistreat or
under treat for a long period of time without Carefully reevaluating the current treatment and making
necessary adjustments.

Need for Dosage Adjustment

In addition to patients’ failure to respond, therapists commonly encounter situations in which the patient
has shown a positive response, but the symptomatic improvement is only partial. Many patients who
show partial response can experience enhanced improvement when doses are increased or medications
are augmented. In such cases of partial response, a re-referral is warranted.

Unexplained Relapse

Sometimes a patient who has responded well to psychotropic medication treatment will, at some point,
experience the reemergence of symptoms—even when medications are continued. When this occurs, the
clinician should consider the following common reasons:
 Failure to comply with treatment; for example, the patient has not been taking medication as
prescribed. The patient has started to drink alcohol excessively, which may exacerbate
depression or anxiety symptoms, interferes with sleep, and may also interfere with metabolism of
the psychotropic medication. Other substance abuse may account for increased symptomatology
(e.g., caffeine disrupting sleep). The patient has experienced a significant increase in
psychosocial stressors.
 A medical condition has developed that may contribute to the development of psychiatric
symptoms, such as thyroid disease.
  “Breakthrough symptoms”: At times the underlying neurochemical disorder or metabolic activity
of the individual undergoes a change that results in a reemergence of symptoms. In many cases
of breakthrough symptoms, a dosage adjustment (usually an increase in dose) may be successful.
 Tolerance to the drug can develop. This is uncommon; however, there is increasing evidence that
some medications work well in early stages of some biologically based mental illnesses but are
not as successful in later phases of the illness. For example, lithium is very effective in early
episodes of bipolar disorder but is less effective after a number of episodes. This probably does
not represent true “tolerance” but, rather, a change in the underlying pathophysiology or
neurochemical substrate.

Onset of New Medical Conditions

A patient may initially be able to tolerate and safely take psychotropic medications; however, the onset
of certain physical conditions can change this, necessitating a re- referral. Such conditions include
pregnancy, epilepsy, certain types of glaucoma, and physiological changes associated with aging and
kidney disease. Another time to reevaluate medications occurs when the patient has an upcoming
surgery, since psychotropics can interact with anesthetics administered before or during surgery and may
also inhibit the healing process. Likewise, new prescription and over-the-counter medications added to
cope with coexisting medical problems can cause drug interaction problems. This is frequently seen in
elderly patients, who often have a host of medical problems and take many medications.

Side-Effect Problems

All psychotropic medications have side effects to a greater or lesser degree. Some side effects are minor,
benign, and transient. Others are quite unpleasant and at times dangerous. Summarized in figure 22-A
are the most common side effects associated with the various classes of psychotropic medications. These
are classified into three groups: Minor or benign: Many of these side effects diminish or disappear with
continued treatment as tolerance develops. Troublesome side effects: These can cause moderate levels of
discomfort and may result in poor compliance. Potentially serious side effects: These may cause
excessive discomfort and can actually be dangerous. A re-referral is warranted in cases where side
effects are troublesome or potentially serious, or when clinical signs of drug toxicity appear.

When It Is Time to Discontinue

Once a patient has fully recovered, the question of when to stop medication arises. Often, even if the
patient is asymptomatic, an abrupt discontinuation of medications can result in either relapse or
withdrawal symptoms. The matter of when to stop is highly individual and depends heavily on three
factors:
 The patient’s history of previous episodes your assessment of the patient’s vulnerability to
relapse. The patient’s feelings about discontinuing medications. each case must be evaluated
individually.
 It is important to note that people treated with benzodiazepines will develop a tolerance to the
medication, and if it is abruptly discontinued, they will have withdrawal symptoms—some of
which can be serious.
 Slow tapering of doses is required and almost always can be safely accomplished.
 In general, it is wise to withdraw all psychotropic medications gradually; for example,
antidepressants should be withdrawn gradually over a period of four to eight weeks.
 A re-referral to the prescribing physician is warranted when, in your judgment, it is time to begin
discontinuing treatment.
 Finally, from start to finish, ongoing collaboration and communication between psychotherapist
and physician is important. Even at times when no problems exist, you may simply want to
update the physician on the patient’s progress.