Polypharmacy has several definitions, including when a patient is prescribed more than four medications. Here, I use the expression for when physicians prescribe an excessive number of psychiatric medications. This is more likely to occur when it is done without research evidence that such combinations are of any added benefit or when less dangerous add-on treatments are available. The clinical consequences of polypharmacy can be increases in nonadherence, adverse drug reactions, drug-drug interactions, risk of hospitalization, medication errors and cost. There was an effort in the field of psychiatry in the early 1980s to discourage polypharmacy. However, since that time, polypharmacy has increased fairly dramatically in psychiatry, even at major psychiatric centers. Despite a huge increase in multiple psychotropics being given at the same time, there is only a small amount of controlled research limited to certain combinations to show that multiple psychiatric medications are necessary or beneficial.
Anti-psychotic polypharmacy is quite common although there is virtually no controlled research on this issue and very little evidence that using more than one anti-psychotic is ever indicated. There are only a few studies of using more than one anti-depressant at the same time. Some have found benefit in carefully selected patients. It is fairly common practice in psychiatry to use more than one psychiatric medication for bipolar patients, although ideally the medications should be from different families, e.g. no more than one anti-psychotic, one seizure medication, or one anti-depressant. Also, lithium monotherapy has been abandoned by many psychiatrists despite evidence that it is superior to much of the polypharmacy replacing it. In the treatment of psychotic depression, controlled studies usually find a single, well chosen anti-depressant works as well as an anti-depressant plus and anti-psychotic.
The use of two or even three psychiatric medications at the same time can be of value. It is often difficult to tell whether this is true without examining a person's record over time and periodically trying cautious decreases in medications that might be superfluous or no longer needed. Unfortunately, sometimes there is the tendency to just add another medication without discontinuing one that is not working or that is only partly beneficial. In my opinion, it is usually best to discontinue or phase out a medication that is being of inadequate benefit and try a second medication by itself before considering restarting the previous medication to see if combination therapy is better.
It is also unclear how many patients are being needlessly loaded up on multiple psychiatric medications. But the one recent report on the previous webpage with patients of four and even five different psychotropic medications is of great concern. It is probably a rare exception. I certainly hope so.
Multiple Anti-Psychotic Drugs Appear to Slow Recovery: In a retrospective study, 70 psychotic patients who were on multiple antipsychotic drugs for at least 3 consecutive days were evaluated for initial, maximum, and final total daily antipsychotic dose and matched with 70 similar patients were being treated by antipsychotic monotherapy. The median total final antipsychotic dosage was 78% higher in the polypharmacy group despite the fact that initial dosages were similar between groups. The median length of hospital stay was also 55% (8.5 days) longer for the polypharmacy group. Clinical improvement was approximately equivalent between the 2 groups. Premorbid pathologic condition was estimated as being approximately equal. Adverse events were also numerically greater in the polypharmacy group. Multiple Versus Single Antipsychotic Agents for Hospitalized Psychiatric Patients: Case-Control Study of Risks Versus Benefits. Centorrino F, Goren JL, Hennen J, Salvatore P, Kelleher JP, Baldessarini RJ. American Journal of Psychiatry. 7/2004;161(4):700-706
Atypical Polypharmacy Rampant at West Virginia Hospital: An excellent 2001 study studied 206 patients treated over a 60 day period with anti-psychotics. 41% received more than one anti-psychotic simultaneously. Psychiatrists reported that they were doing it primarily to increase the anti-psychotic impact (59%). Psychiatrists reported thinking that the majority of patients so treated were being helped by the polypharmacy. Patients were often receiving sub-optimal doses of the anti-psychotics. There is absolutely no research supporting this very common nationwide practice. The concern is that it needlessly increases side-effects and results in patients taking medicines that are not working well for them. 51% of records did not document why the patients were receiving the polypharmacy. WVU. Multiple antipsychotic medication prescribing patterns. Schumacher JE, Makela EH, Griffin HR. Ann Pharmacother. 2003 Jul-Aug;37(7-8):951-5
Study Finds Polypharmacy a Common Cause of Hospitalization: 347 patients (aged 16-97) on a mean of 7.4 medications. 10.8% of the study population had Drug Related Problems (DRPs) on admission, 71.9% of which were dominant reasons for admission. DRPs contributed partly in the remaining cases. These DRPs were mostly avoidable, and can be broadly classified into non-compliance, adverse drug reactions, require synergistic therapy, inappropriate dose and untreated condition. 52% of these cases were made up of geriatric patients. No statistical difference was found between patients on polypharmacy and those on major polypharmacy (10 and more drugs) in having a DRP. DRPs contributing to hospital admission appeared to be avoidable. Geriatric patients were more susceptible. Therapy related hospital admission in patients on polypharmacy in Singapore: a pilot study. Koh Y, Fatimah BM, Li SC. Pharm World Sci. 2003 Aug;25(4):135-7. Singapore
Swedish Study Finds 20% Receiving More than One Antipsychotic: A study by Uppsala University of 519 out-patient visits in which anti-psychotic were prescribed found that on 20% of the visits more than one antipsychotic was used. Patients on one antipsychotic averaged only 211 chlorpromazine equivalents of medications while those on more than one average 407 equivalents. The authors state that "antipsychotics, in contrast to current recommendations, were prescribed as highly individualized therapies in a wide variety of doses and with a high frequency of polypharmacy. The combinations used are often unsuitable and may lead to unnecessary adverse effects." Dosage patterns of antipsychotic drugs for the treatment of schizophrenia in Swedish ambulatory clinical practice--a highly individualized therapy. Bingefors K, Isacson D, Lindstrom E. Nord J Psychiatry. 2003;57(4):263-9
11More than a quarter (N = 138) of unipolar depression patients (N = 494) were currently prescribed an antipsychotic; 40% of these received an antipsychotic without any recognized indication. The mean time on antipsychotic therapy was 3 years. Patients on antipsychotic therapy were, on average, taking twice as many total medications as those not on antipsychotic therapy. Patients with psychotic depression were taking an average of nearly twice the antipsychotic dose of nonpsychotic patients. Current clinical guidelines commend careful antidepressant choice in preference to polypharmacy. New York. Conventional antipsychotic prescription in unipolar depression, I: an audit and recommendations for practice. Wheeler Vega JA, Mortimer AM, Tyson PJ. J Clin Psychiatry. 2003 May;64(5):568-74 Ed: All 28% of depressed patients on anti-psychotics should have been first tried on an anti-depressant without an anti-psychotic. Research shows that the large majority of psychotically depressed patients will improve just as fast on a good anti-depressant alone as with the addition of an anti-psychotic. Also, thyroid and folate medications as well as fish oil, exercise, and possibly bright light are much safer ways to boost the effect of the anti-depressant. rTMS may also be of value.
Review of Combination Studies Find Combination Best for Acute Mania: For acute mania, controlled studies find an antipsychotic drug with a mood-stabilizer helpful. The combination of lithium and valproate, even though widely used for acute mania, is lacking in controlled data. For acute bipolar depression, the controlled combination studies reviewed fail to show clear advantages in efficacy of an antidepressant with a mood-stabilizer versus two stabilizers or one mood-stabilizer alone. Large, controlled, randomized, long-term studies with modern antidepressants are not available. Controlled combination studies of mood-stabilizers suggest gains in efficacy over monotherapy in the long-term treatment of bipolar disorder. Controlled combination studies in bipolar disorder are uncommon. Increased attention should be given to study combination treatments in all phases of bipolar illness to determine the most efficacious and safest combinations. NIMH. Combination treatment in bipolar disorder: a review of controlled trials. Zarate CA Jr, Quiroz JA. Bipolar Disord. 2003 Jun;5(3):217-25. Ed: In view of the huge increase in suicide deaths on valproate and the lesser increase on carbamazepine, lithium is clearly still the "gold standard." NIMH fails to cover the earlier studies showing thyroid a useful adjunct for bipolars. Lithium plus carbamazepine is a proven combination but whether valproate adds to lithium is unclear.
Polypharmacy Up Dramatically in Last 20 Years: A review of 28 studies documents a huge decline in the rate of psychiatric monotherapy from 47.8% in the 70s to only 19.6% in the 90s. The mean number of psychotropic drugs prescribed rose from 2.2 to 2.9 and the number of patients receiving > or = 3 psychotropics rose from 27.5 to 49.7%. The use of drug monotherapy in psychiatric inpatient treatment. Rittmannsberger H. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr;26(3):547-51
27% Discharged on Two or More Anti-Psychotics: A Canadian study of 229 hospital discharges found 27% were sent home on at least two different anti-psychotics. The practice is called controversial by the authors and lacking any type of evidence-based support. Antipsychotic polypharmacy: a survey of discharge prescriptions from a tertiary care psychiatric institution. Procyshyn RM, Kennedy NB, Tse G, Thompson B. Can J Psychiatry. 2001 May;46(4):334-9
Polypharmacy at NIMH Skyrockets: The use of more than one psychotropic for mood disorders has dramatically increased at NIMH. The percentages of patients discharged on treatment with 3 or more medications were 3.3% (1974-1979), 9.3% (1980-1984), 34.9% (1985-1989), and 43.8% (1990-1995). No correlation was found between polypharmacy and age. Patients more recently discharged from the NIMH had an earlier age at illness onset, more lifetime weeks depressed, and a higher rate of rapid cycling than patients in the earlier cohorts. Some of the increase may be due to more difficult patients being treated, but the degree of improvement at discharge did not improve in later years vs. earlier ones. However, the authors conclude, "More systematic approaches to the complex regimens required for treatment of patients with refractory mood disorder are clearly needed." The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study. Frye MA, Ketter TA, Leverich GS, Huggins T, Lantz C, Denicoff KD, Post RM. J Clin Psychiatry. 2000 Jan;61(1):9-15
Five Psychotropics at the Same Time as Common as Monotherapy in Austria: An incredible report from a psychiatric university clinic, the psychiatric department of a general hospital and a regional mental hospital in Austria found between 5% and 22% of all patients were being given five psychiatric medications at the same time while only 8% to 22% were being treated with a single psychiatric medication. The authors note that most experts favor monotherapy. Polypharmacy in psychiatric treatment. Patterns of psychotropic drug use in Austrian psychiatric clinics. Rittmannsberger H, Meise U, Schauflinger K, Horvath E, Donat H, Hinterhuber H. Eur Psychiatry. 1999 Mar;14(1):33-40