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The TIMA Bipolar Algorithm

DEFINITION – An algorithm (pronounced AL-go-rith-um) is a procedure or formula for solving a problem. )

Algorithms represent an attempt to replace shoot-from-hip psychiatry with step-by-step guidelines representing expert consensus, though they are not meant to replace empirical clinical judgment. Algorithms were pioneered by the Texas Medication Algorithm Project (TMAP), which issued its first guidelines for bipolar disorder in 1998, with a revision in June 1999. In Oct 2001, TMAP came out with the “roll out phase” of its bipolar algorithm, Texas Implementation of Medical Algorithms (TIMA), involving the wide-scale training of clinicians for use in the public sector.

As an illustration of what a difference two years make, 1999’s algorithm listed a choice of Depakote or lithium for patients presenting with mania or hypomania, and Tegretol or Depakote for mixed episodes or rapid-cycling. It was a full five stages down, at desperation level, just before ECT was considered as an option, that an atypical antipsychotic such as Zyprexa was first mentioned, and only as an add-on. By contrast, TIMA has Zyprexa right at the top, as a first choice stand-alone treatment for either euphoric mania/hypomania, mixed or dysphoric mania/hypomania, or psychotic mania.

The new guidelines also give first-time recognition to Lamictal for treating bipolar depression, and to Trileptal, similar chemically to Tegretol but with fewer side effects. Significantly, TIMA lists its goals as “symptomatic remission, full return of psychosocial functioning; and prevention of relapses and recurrences,” all which imply there are smarter ways to use the medications available to us.

The TIMA project is headed up by Trisha Suppes MD, PhD and Ellen Dennehy PhD, both who were lead authors in the earlier TMAP algorithm. In addition, a report on TIMA in April’s Journal of Clinical Psychiatry lists an all-star roster of authors including Alan Swann, Charles Bowden, Joseph Calabrese, Robert Hirschfeld, Paul Keck Jr, Gary Sachs, M Lynn Crismon, Marcia Toprac, and Steven Shon.

Critics have accused TMAP algorithms of being Trojan horses underwritten by the pharmaceutical industry to get their brand name drugs used in state mental health programs in place of cheaper generics (see article). Clearly the drug companies have a stake in getting TMAP implemented as widely as possible, with vast sums invested in state political campaigns and lobbying efforts. But flawed as TIMA may be, patients can benefit from knowing what model treatment is supposed to look like, bearing in mind the recommendations are no substitute for what you and your psychiatrist may decide:


TIMA stresses the primacy of the mania/hypomania algorithm, even when bipolar depression is involved. For patients presenting with euphoric mania/hypomania or psychotic mania, the choice is between lithium, Depakote, or Zyprexa. For mixed or dysphoric mania, Depakote or Zyprexa are the two options. TIMA distinguishes between divalproex and valproic acid, recommending the former due to “significantly better tolerability.” (Abbott Laboratories’ Depakote is divalproex sodium.)

For a partial response with good tolerance, the recommendation is to move to combination therapy with two of the following: lithium, Depakote, or Trileptal, or one of the same three mood stabilizers plus either Zyprexa or Risperdal. For stage three, the physician is asked to keep one agent from the previous combination and change to a different drug out of the same group. In stage four, Seroquel and Geodon are added as options (as part of a two-med cocktail), and in stage five we graduate to a three-med combination, with lithium plus one of the anticonvulsant mood stabilizers plus one of the atypical antipsychotics. At stage six, the option is ECT or adding Clozaril. At stage seven, the algorithm begins to lose clarity with “other” options as add-ons, including Lamictal, Topamax, and conventional antipsychotics..

Bipolar Depression

For bipolar depression, TIMA’s emphasis is on treating the patient for hypomania and mania, using its depression algorithm as a concomitant treatment strategy. Accordingly, stage one for both the mania/hypomania and depression algorithms are the same, using a mood stabilizer or Zyprexa. Stage two adds an SSRI, Wellbutrin, or Lamictal to the existing medications. TIMA implicitly concedes it is stepping out on a limb for its stage one and stage two recommendations by acknowledging that stage three “begins to rely more heavily on clinical consensus and expert opinion.” Even so, “there is only limited data on treatment of bipolar depression following failure in stage two.” Stage three offers the choice of adding lithium or switching to an alternate antidepressant including Effexor or Serzone or adding an antidepressant (for a double combination). The double combination extends into stage four, with Lamictal considered an antidepressant for TIMA’s purposes. In using a combination, TIMA suggests antidepressants from different classes (eg an SSRI plus Wellbutrin). Stage five involves switching to an MAOI or adding an atypical antipsychotic. Stage six represents the kitchen sink, from ECT to tricyclics to omega 3 to acupuncture to hormones. (MAOIs are preferred over tricyclics, possibly because of greater risk of tricyclics causing switches into mania, and for the purported efficacy of MAOIs in treating atypical depression, which seems to seems to manifest in bipolar patients, though TIMA doesn’t state this.)

Decision Points

Week two into treatment involves the first critical decision point for physician (and presumably the patient), building up to weeks six and eight, where moving to the next phase of treatment needs to be considered should symptoms persist. TIMA recommends that if a medication is to be discontinued, the new medication should be started and brought to a therapeutic level, then the medication to be discontinued should be gradually tapered over a period of at least one month (unless the side effects from the first drug increases, in which case, according to TIMA, the taper should begin earlier).

Side Effect Management

GI upset: Take medication with food and large amounts of liquid; consider lowering the dose; use sustained release preparations when available; use histamine blockers such as Tagamet and Zantac.

Mild tremor: Decrease dose; add 20-30 mg propranolol (a beta-blocker).

Parkinsonian tremor: Decrease dose, divide dosing; add one to two mg benztropine, 100 mg amantadine (both anti-Parkinson’s), or 25-50 mg Benadryl.

Sedation: Change dosing schedule

Extrapyramidal (tics, tremors, etc): Reduce dose; 20-30 mg benztropine, amantadine, or Benadryl for akathisia, or clonidine (an anti-hypertensive) or lorazepam; one mg benztropine for preventing or managing dystonia or one mg lorazepam for managing dystonia.

Tardive dyskinesia: Lower dose; vitamin E in high doses (1,000 units/day) may help.

Insomnia: Change dosing schedule; add 5-10 mg Ambien, 10 mg Sonata, or benzodiazepine.

Sexual dysfunction: Use 4-7.5 mg yohimbine three times a day, 4-8 mg cyproheptadine (a hay fever drug) shortly before sexual intercourse, or 75-300 mg/day Wellbutrin.

The Continuation Phase

Mania/Hypomania: TIMA recommends simplifying the medication regimen, with gradual tapering, though it notes “little is scientifically known about the relative need for combined mood stabilizers long term.” Continuation with mood stabilizers is recommended for those who underwent ECT in the initial phase of treatment. TIMA recommends a lifetime regimen of mood stabilizers for those who have had two manic episodes, or one severe episode with a family history of bipolar or major depression. For a patient with one episode and no family history, medication and tapering may be considered six months into remission (allowing for individual circumstances).

Bipolar depression: Here TIMA enters into controversy by recommending tapering and discontinuing antidepressants one to three months after full remission for first-time depression patients. (For a full discussion, see article.)

Drug Interactions

TIMA goes into considerable detail, noting that caffeine is one of the drugs that may lower lithium levels. This report will restrict itself to the depression and bipolar drugs that may interact with each other, including:

Depakote: Increases Lamictal levels, may increase tricyclic levels and possibly SSRIs. May be decreased by Tegretol. May be increased by SSRIs.

Tegretol: Can induce the metabolism of Lamictal, Depakote, benzodiazepines, and tricyclics. Trycyclics may decrease Tegretol levels. Using Tegretol with Clozaril is not recommended.

Zyprexa: Elevated levels when used with Luvox. Fifty percent increase in clearance from the system when used with Tegretol.

Clozaril: Luvox and Serzone may raise levels and inhibit its metabolism.

Seroquel: Luvox and Serzone may increase blood levels. Tegretol may decrease blood levels.

Geodon: Tegretol will decrease levels.

Topamax: Can potentially decrease Depakote levels. Depakote and Tegretol appear to decrease Topamax levels.

Lamictal: Depakote inhibits its metabolism; therefore Lamictal should be increased slowly when these medications are combined. Tegretol induces the metabolism of Lamictal; therefore higher doses of Lamictal are required when used with Tegretol.

Prozac: Results in increased concentrations of tricyclics, antipsychotics, and Tegretol. Should not be taken with MAOIs or in a patient who has recently discontinued an MAOI.

Paxil: Causes increased tricyclic levels.

Zoloft: Causes increased tricyclic levels.

Wellbutrin: Should not be given with MAOIs.

Serzone: Can increase plasma concentrations of MAOIs, Haldol, and benzodiapines.


Do you know why you are taking every medication in your cocktail, what symptom it is treating, in which phase, for how long it is expected to be taken, its benefits vs risks, and how it complements and interacts with the other drugs? Does your doctor or psychiatrist know?

You are entitled to straight answers.
SOURCE:- directly from McMan’s Depression and Bipolar Website

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