Treating Psychiatric Difficulties with Medication

by Wayne Creelman, M.D.

When patients are admitted for inpatient care at Pine Rest, it is usually for one of two psychiatric difficulties. Either the individual is suffering from an affective disorder, meaning they are severely depressed or struggling with control issues relating to a manic depressive disorder, or they are suffering from the signs and symptoms of a psychotic disorder.

Affective and Depressive Disorders
Depression is clearly the most common reason patients require hospitalization at Pine Rest. One of the most important steps in treating an individual suffering depression is making the correct diagnosis. Depression can occur for a variety of reasons, including a drug-induced depression, dementia, anxiety, a prolonged grief reaction, or simply as a consequence of medical illness. Seventeen percent of the United States population reports a major depressive episode in their lifetime, with the average age of onset in the late twenties. Fifty percent of patients have their first episode by age 40, and the duration is typically six months to two years if left untreated. Episodes of depression will continue in up to 80% of individuals who do not receive treatment. Unfortunately, depression is a chronic illness. For the first episode of a significant major depression, the probability of a recurrent episode is 50%. After the second episode the probability of a relapse jumps to 80%. After the third episode, that probability increases to over 90%. The financial impact of depression is extraordinary. The estimated annual cost in the United States exceeds $60 billion per year. These costs include the dollars associated with decreased productivity, death from suicide, pharmaceutical treatment, outpatient/partial care, inpatient care, and absenteeism (lost work days).

There are several risk factors for depressive disorder including family history of depressive disorders, a prior history of a depressive disorder, the female gender, life stressors such as bereavement or chronic financial problems, as well as certain personality traits. The death of parents, childhood abuse, anxiety disorders, neurologic disorders including Parkinson’s, Alzheimer’s, and stroke difficulties, as well as primary sleep disorders all tend to increase the likelihood of an individual suffering a depressive illness.

Medical Treatment of Depression
There have been some major developments in the medical treatment of depression over the years, beginning in the 1930s when electroconvulsive therapy was the mainstay for minimizing depressive episodes. The tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) were developed in the 1950s with further refinement of pharmaceutical agents coming in the 1980s, including the selective serotonergic reuptake inhibitors (SSRIs), and more recent pharmacologic refinements in the 1990s.

When a psychiatrist makes a decision to begin medication management for depression, there are several factors that need to be considered in an antidepressant selection. Safety is the foremost concern as a consequence of drug-drug interaction potentials. Tolerability is also important for compliance reasons, both for acute prescription as well as long-term usage. Efficacy issues including onset of action, as well as the treatment and prevention/maintenance phase of medication management are also important. Cost has also become a major issue, with generic drugs lessening the expense of brand name preparations. Lastly, the simplicity of dosing and need for monitoring blood levels must also be considered.

If an ideal antidepressant was available to the psychiatric community, it would have seven characteristics including a rapid onset of action, an intermediate half-life, a defined therapeutic blood level, no side effects, minimal drug interactions, low toxicity associated with overdose, and a broad spectrum of efficacy. Unfortunately, no ideal antidepressant exists. Instead, the psychiatric community has four major categories of medications for major depression. These categories include tricyclic antidepressants, MAOIs, SSRIs, and heterocyclic agents (e.g. Trazodone).

Tricyclic antidepressant medications have been around the longest and have demonstrated efficacy that has been unsurpassed by newer agents. Unfortunately they can be lethal in overdose. They have a very narrow therapeutic index as well as a very high potential for cardiac side effects. Their tolerability can become problematic as they create sedation, weight gain, low blood pressure, sexual dysfunctions, and can lower the seizure threshold. For all of the above reasons, psychiatrists do not use tricyclic antidepressants very often since their only real advantage in today’s marketplace is their extremely low cost.

MAOIs are very specialized antidepressants that work in populations of atypical depressed patients who tend to note depressive changes in their appearance or in dysfunctional behaviors like increasing their time sleeping and/or increasing their food intake. MAOI medications, including Parnate and Nardil, work well in depressed patients who are able to tolerate dietary restrictions requiring the avoidance of all foods containing high levels of tyramine due to the potential risk for hypertensive crisis. Tolerability can also be a problem because MAOIs also cause low blood pressure, weight gain, and sexual dysfunctions that are more common than with tricyclics.

Heterocyclic agents like Trazodone that block a variety of receptor sites have been found to be helpful in certain populations with whom sedation is a desirable side effect. Wellbutrin is an antidepressant that shares a chemical structure very similar to amphetamines, which may be why it has a more energizing action in individuals who are depressed.

The last category of antidepressants receiving the most press recently is the serotinergic antidepressants. The therapeutic profile includes actions that are antidepressant, anti-obsessive compulsive, anti-panic, and anti-bulimic. Five agents currently available in the United States are Citalopram, Fluvoxamine, Sertraline, Fluoxetine, and Paroxetine. All of these medications act in the exact same way, but have different parameters with respect to dosage ranges, absorption time, and side effect profiles. In general SSRIs are as effective as other antidepressants. With respect to safety issues, they have a greater risk/benefit ratio compared with tricyclics and MAOIs because they are safe in overdose and demonstrate virtually no systemic or cardiac side effects. Tolerability is less problematic, although common adverse events include nausea, loose stools, tremor, and dry mouth. Central nervous system symptoms can include anxiety, agitation, and insomnia. Lastly, sexual dysfunctions can include ejaculatory disturbances in men and anorgasmia in women. Some of the most common side effects of Paxil are nausea, headache, and insomnia. Prozac’s (Fluoxetine) more common side effects include nausea, headaches, and nervousness, while Zoloft’s more common side effects include nausea, headaches, and dry mouth. The SSRIs and the newer agents clearly offer an opportunity to effectively treat depressive disorders in an extremely successful fashion. Once appropriate dosing is established, patients usually return to their baseline status of functioning after 4-6 weeks.

Psychosis and Psychotic Disorders
The second reason why patients are admitted to Pine Rest is as a result of a psychotic disturbance, which essentially means their ability to test reality has become compromised. The most common psychotic disturbance is schizophrenia. The socioeconomic impact of schizophrenia is extraordinary. One percent of the American population is affected by this illness. Twenty-five percent of all hospital-bed days, 40% of all long-term-care days, and 20% of all Social Security Benefit days are a consequence of schizophrenia. Cost exceeds $40 billion per year in the United States. The features of schizophrenia spread over five areas. Positive symptoms include delusions, hallucinations, disorganized speech patterns, and catatonia. Negative symptoms include difficulty relating to others, lack of spontaneous speech, anhedonia, and social withdrawal. The social/occupational dysfunction associated with schizophrenia includes work problems, difficulties in interpersonal relationships, and compromise in the ability to carry on self-care responsibilities. Cognitive deficits associated with this illness include problems with attention, memory, and executive functions like the ability to abstract. Co-occurring conditions also arise including mood difficulties, substance use disorders, anxiety syndromes, and, at times, acting out aggressive behaviors.

Traditional antipsychotic medications called “typical agents” are used to treat individuals suffering from psychotic disorders. These medications have high potency or low potency based on milligram dosing. The high potency agents cause major problems with neurological side effects while the low potency agents cause more difficulties with sedation. Typical agents include Haldol, Thorazine, Navane, Prolixin, and Stelazine.

Newer antipsychotic agents are characterized as “atypical” agents. Newer agents are safer and have a higher tolerability than the older traditional medications. These have a lower incidence of abnormal muscle movements, a broader efficacy profile, and minimal effect on prolactin levels. This all translates into fewer side effects for the person using the medication. These medications are more effective because they minimize both the positive as well as the negative symptoms of schizophrenia. They have a unique receptor binding profile, which includes significant blocking of dopamine as well as serotonin in the brain. The combined blockade of both of these neurotransmitters allows for greater therapeutic efficacy.

The newer atypical antipsychotic agents include Clozapine, Olanzapine, Quetiapine, Risperidone, and Geodon. The first of the atypical agents available to the public was Clozaril, which continues to be used today. Unfortunately, regular blood monitoring is required due to very serious and lethal reports of aplastic anemia, making the use of this medication more cumbersome.

Quetiapine, or Seroquel, is extremely effective in the treatment of positive and negative symptoms of psychotic disorders including schizophrenia. It is well tolerated and has a good safety profile with no routine blood monitoring required. It also has a low potential for drug interactions and rare muscle movement difficulties arise with its use.

Risperdal is an alternate atypical antipsychotic that has been around for over 10 years, demonstrating excellent efficacy at dosages averaging 4-6 milligrams per day. It is a safe and effective treatment for positive and negative symptoms of schizophrenia and psychosis.

Olanzapine (Zyprexa) is a superior medication for overall treatment of negative symptoms of psychosis. The very low likelihood for any acute abnormal muscle movement symptoms or irreversible abnormal muscle movements, low prolactin elevations (certainly less than Haldol or Resperidone) offers a very favorable safety profile.

Lastly, Geodon, the most recently released antipsychotic medication, has already proven to be an excellent agent for the treatment of both positive and negative symptoms of schizophrenia.

When using any of the antipsychotic medications, it is important to recognize that each patient’s plasma level concentration of a drug will be unique to that individual’s obtaining a maximum treatment response. Below a therapeutic range will result in either minimal or partial therapeutic effects, and typically, dosing above that therapeutic level will create side effects or toxicities with no additional efficacy. This is why it is essential to monitor the prescription and dosage of these medications very carefully, regularly, and with full involvement of the individual receiving these medications.

Because the consequences of depression as well as psychotic disorders can include suicidal behavior, it is extremely important to protect individuals when they are suffering in a psychiatric state that does not allow them to make rational decisions about their activities of daily living. That is why inpatient hospitalization will always be an option and part of the continuum of psychiatric care. The typical length of inpatient hospitalization rarely exceeds one week, after which the individual is linked to an outpatient psychiatrist/therapist for continuing care in Pine Rest’s outpatient clinic network.