C.O.P.E.S.

Stepped Care for Depression in Primary Care

The C.O.P.E.S. Model was developed to improve collaboration between patients, the behavioral health department, primary care providers and the emergency department at Susquehanna Health. C.O.P.E.S. is an acronym for

Collaboration between Outpatient and Inpatient Behavioral Health, Primary

Care, and the Emergency Department at Susquehanna Health. This model was developed as part of an evidence-based Doctorate of Nursing Practice Project at Chatham University by Stephanie King, DNP, PMHNP-BC, CRNP

STEPPED CARE FOR DEPRESSION IN PRIMARY CARE

As part of our ongoing focus of expanding access to behavioral health services, we are working to develop tools and interventions to create a more collaborative relationship with other SH providers and departments. As such, we have created this stepped care algorithm manual to assist you in initiating depression treatment in your patients. Because of considerable variation in each patients clinical circumstances, it is not possible to specify a treatment algorithm that will be a perfect fit for each patient. The stepped care treatment algorithm outlined in the next few pages provides a general guideline to be followed in treating depressed patients. Within this guideline, the treatment team will have to use clinical judgment to ensure that patients enter the stepped care algorithm at the correct step and that each patient has a treatment plan that is best suited for his or her clinical circumstances. We have also noted recommendations for consult with the psychiatrist or psychiatric nurse practitioner as appropriate. The recommended stepped care algorithm is evidence-based and was adapted in part from the Project IMPACT Intervention Manual and the DSM-5 and is based on a number of consensus statements and treatment guidelines for depression in primary care including: AHCPR Treatment Guidelines for Depression in Primary Care (AHCPR) Treatment recommendations by a consensus panel convened by the American Association for Geriatric Psychiatrists (Am J Geriatr Psychiatry) and a Consensus Statement on Late-Life Depression by the DBSA (Depressive and Bipolar Support Alliance; 2002) Treatment Guidelines for Major Depression by the American Psychiatric Association

The ultimate goals of treatment are to (a) achieve symptomatic remission and full return of psychosocial functioning and to (b) prevent relapse and recurrence of depression.

Acknowledgements This manual was adapted in part from the IMPACT Intervention Manual as developed by Jrgen Untzer, MD, MPH and Sabine Oishi, MSPH with help from Rebecca Shoai, Christine Smith and Monica Della Ripa, MA.

Stepped Care Treatment Algorithm

Step 1(8-10 weeks)(p4)
(1) Check TSH2 (2) Start first line antidepressant (AD) or Problem Solving Treatment (PST-PC)

Antidepressant (AD)
(Usually an SSRI titrated to therapeutic dose)

OR

PST-PC
(if patient strongly prefers psychotherapy)

Evaluate response to step 1 treatment.

Patients with full response go to maintenance treatment. Others go to step 2

***(Before moving to Step 2, please ensure AD titrated to therapeutic dose)***

(AD in step 1)

(PST in step 1)

Step 2 (p5)
(4-8 weeks)

Partial response to step 15 Different AD type6 or Augment AD7

No response 5 PST-PC or Different AD type6

Partial response5 Add 1st line AD

No response5 1st line AD

Evaluate response to step 2 treatment. Patients with full response go to maintenance treatment. Others are considered for step 3.

Step 38
Consider

Trial of a 2nd or 3rd type of antidepressant. Combination of antidepressant and PST-PC (if not already tried in step 2) Other augmentation of antidepressants (if patient has had a partial response to an antidepressant in step 2)7 Referral to specialty mental health care for

ECT (especially if depression is severe or if patient has psychotic symptoms, poor po intake, or high risk of suicide) Treatment of comorbid psychiatric disorders (for example OCD, Panic disorder, PTSD) Other types of psychotherapy not available in primary care such as CBT, IPT, or family therapy.

Additional Treatments to be considered during the course of the program9.

1

Step 1

Step one treatment is generally initiated in the primary care clinic in collaboration with the patients regular primary care provider. It will be the initial treatment step for the vast majority of patients. Only the occasional patient who has just completed and failed what appears to be an adequate trial of step one treatment should be considered to start at step two in consultation with the team psychiatrist (see below).
2

TSH Testing:

Because of the a relatively high prevalence of hypothyroidism in adults (particularly in older women) and because hypothyroidism can contribute to a depressive syndrome, primary care providers will be encouraged to order a TSH test in patients who have not had a normal thyroid test within the past 6 months. Patients who are hypothyroid should be considered for thyroid hormone replacement by their PCP.
3

Initial Treatment Choice

In most cases, patients will be started on an antidepressant medication, usually a selective serotonin reuptake inhibitor (SSRI) (see section D1 on pages 11+12). Patients who have previously failed or not tolerated an adequate trial of an SSRI will be considered for an alternative antidepressant (see below). Patients who have previously responded to an antidepressant from a different class should be restarted on the previous antidepressant whenever possible. Secondary amine tricyclic antidepressants (TCAs) such as nortriptyline or desipramine should be considered for patients who find the price of an SSRI to be a significant financial barrier to antidepressant treatment unless a TCA is clinically contraindicated (see section D). Unless there are significant financial barriers, SSRIs are a preferred choice over TCAs at this step because of their lower rates of side effects, particularly in older adults. Section (D), compares TCA and SSRI side effects across a large number of clinical trials.

Patients who prefer psychotherapy may be started on problem solving tratment (PST-PC) in step 1.
4

Titration of initial treatment.

Antidepressants should be started at low doses and titrated to a therapeutic dose over a period of 4-6 weeks. See section (D2 page 12) for recommended titration schedules. If patients cannot tolerate a particular treatment (i.e., intolerable side effects even with careful titration and clinical management), consider a switch to an alternative antidepressant or PST-PC after 2-4 weeks and restart step 1. Strategies for managing common side effects of antidepressants are outlined in section (D5 on pages 13 + 14).
5

Treatment response:

An adequate trial of step 1 treatment means that patients have completed an 8-10 week antidepressant trial at a sufficient dose (see section D, for dosing guidelines) or a trial of 6-8 sessions of PST-PC. Patients who have had a full response to step 1 treatment (see below) should proceed to relapse prevention planning and maintenance treatment. Patients who do not

5 have a full response to step 1 treatment should be considered for consultation with the psychiatry department. Unless the psychiatric provider feels comfortable making a clinical recommendation for an alternate treatment plan based on the history, the psychiatrist should see most of the patients at this stage for a one time psychiatric consultation. The following is a general guideline to defining treatment response:

(1) Full response / remission: (a) Major depression: Fewer than 3 / 9 DSM 5 depressive symptoms AND at least a 50
% reduction in the (PHQ-9) score

(b) Dysthymia: Fewer than 2/7 DSM 5 depressive symptoms AND at least a 50 % reduction in the (PHQ-9) score. (2) Partial response:
At least a 30 % reduction in DSM 5 depressive symptoms and the (PHQ-9).

(3) No response: (a) Major depression: 5 or more DSM 5 depression symptoms OR greater than 15 on PHQ-9 (b) Dysthymia: 3 or more DSM 5 dysthymia symptoms OR greater than 10 on the (PHQ-9).
Initial response to antidepressant medications usually occurs within 2-6 weeks. If there is NO response (see above) to antidepressant treatment after 4-6 weeks of an antidepressant at a therapeutic dose, an alternative plan should be initiated. If there is a partial response by weeks 46, a full trial (8-10 weeks) of the antidepressant at a full therapeutic dose is recommended.
6

Step 2 Antidepressant selection

See section D(p11+12) for general information about antidepressant medications. All antidepressants should be started at low doses and titrated upwards towards a therapeutic dose as tolerated over a 4-6 week period. Patients who have failed an adequate trial of 2 first-line antidepressants at step 1 (usually an SSRI) should be considered for a trial of an antidepressant from a different class. The choice of the second agent may vary depending on the clinical circumstances (psychiatric consultation can be helpful with this decision). If the first trial was with an SSRI or if the patient has a severe depression with prominent neurovegetative symptoms, a noradrenergic agent such as Venlafaxine XR, or a tricyclic antidepressant (TCA) such as desipramine or nortriptyline are recommended for a 2nd trial. Caution is recommended if tricyclic antidepressants are used in seniors because they can cause cardiac conduction problems, orthostatic hypotension, anticholinergic side effects, and sedation (see section D5) Tertiary amine tricyclics such as imipramine, amitriptyline, or doxepin should be avoided because of severe side effects in older adults. Older adults who have responded to a tertiary amine tricyclic in the past should be considered for a trial of a secondary amine tricyclic agent such as desipramine or nortriptyline.

6 At this stage, patients may also be considered for a trial of another antidepressant such as Bupropion, Viibryd, Pristiq or Cymbalta.
7

Augmentation Strategies:

In general, augmentation strategies are not preferable as first or second step treatments in primary care because they require closer clinical monitoring, more complex drug regimens, and often greater expense to the patient. There are, however, times when a patient has had a partial response to an initial antidepressant agent and augmentation with either psychotherapy (PSTPC) or another medication is clinically indicated. The team psychiatrist can be helpful with making this decision and with providing guidance on specific augmentation strategies. An exception to this general rule is the addition of low dose Trazodone (i.e., 25- 50 mg po qhs) for insomnia in patients who are on an SSRI. (See also section D5, p13+14), for management of common side effects. Recommended augmentation strategies include:

(1) Combination of an antidepressant and PST-PC (2) Combination of an SSRI and a noradrenergic or dopaminergic antidepressant such as bupropion or a TCA (nortriptyline or desipramine). When SSRIs are combined with TCAs, serum levels of the TCA should be checked to avoid toxicity resulting from drug interactions (see section D6 p 15+16)). At this stage, Seroquel XR or Abilify may also be considered as augmenting medications. For adjunctive treatment in major depressive disorder, Seroquel XR should be initiated at 50mg PO four hours before bedtime for two days, increased to 150mg PO for two days, and then increased to no more than 300mg. It is helpful to discuss possible sedation with your patient when initiating Seroquel, and encourage them to take the medication 12 hours before the time they wish to wake in the morning. Abilify can also be used as an adjunctive treatment for depression and should be initiated at 2-5mg daily.
Additional strategies such as augmentation of an SSRI with a TCA or an SSRI with lithium, augmentation of an antidepressant with a stimulant such as methylphenidate, or augmentation of a TCA or an SSRI with thyroid hormone (especially if TSH is elevated) may be considered in consultation with the team psychiatrist.

Step 3:
Patients who have not had a full response at step 2 should be strongly considered for an extended psychiatric evaluation. At this step the psychiatrist may suggest and initiate a number of treatments in consultation with the patients PCP. The choice of treatment at this step depends on the clinical situation, the resources available, and the patients treatment preferences.

7 Potential treatment strategies for step 3 include

A trial of a 2nd or 3rd type of antidepressant Combination of antidepressant and PST-PC (if this has not already been tried at step 2) Other augmentation strategies (see no. 7 above). This is particularly helpful if the patient has had a partial response to treatment at step 2. A referral for additional treatments in a specialty mental health setting may be indicated for

Electroconvulsive therapy (ECT): This is particularly indicated for severe depression with psychotic symptoms, poor PO intake, or high risk of suicide. ECT should usually be initiated as right unilateral ECT to minimize cognitive impairment, but before declaring a patient refractory to ECT, he or she should have a course of bilateral treatment. The team psychiatrist may introduce the option of ECT earlier in the treatment course if patients are experiencing such severe forms of depression. Specialized treatments for comorbid psychiatric disorders such as OCD, panic disorder, or PTSD, Other types of psychotherapy that are not available in the primary care setting such as CBT, IPT, or family therapy.

Additional treatments to be considered:

Additional treatments that may be considered by the treatment team at any stage in the treatment course include

referrals to self help groups such as AA and NA, referrals to support groups run by the Depression and Bipolar Support Alliance (DBSA), Alzheimers Association, ALANON, or caregiver support groups, referrals to other community resources, referrals to specialty services such as a chronic pain clinic

SOME SPECIAL POPULATIONS

1.

Patients with comorbid anxiety and panic disorders:

In general, patients with comorbid anxiety disorders such as panic disorder can be treated using antidepressants such as SSRIs in primary care. Such patients should usually be started on low doses of an SSRI (such as 10mg of fluoxetine or 20 mg of paroxetine per day) and slowly titrated up to a therapeutic dose as tolerated because the medication can cause a transient worsening of anxiety symptoms. In some cases, the use of a benzodiazepine such as clonazepam or lorazepam is helpful to reduce severe anxiety during the initial weeks of treatment, but the long-term use of such agents is to be avoided because they can result in physical dependence, cognitive and motor impairment, falls, and other accidents. Consultation with the team psychiatrist can be helpful in making treatment plans for patients with comorbid depression and anxiety disorders.

2. Patients with comorbid alcohol or substance abuse. Patients with depression and comorbid alcohol or substance abuse should be considered for treatment of both substance abuse and depression. They should usually be referred for substance abuse specialty treatment as available and to a self-help group such as AA or NA. At times, it is prudent to initiate substance abuse treatment before starting an antidepressant because symptoms of depression may often remit with successful treatment of the alcohol or substance abuse. The decision when to start depression treatment is a complex one, and the team psychiatrist can be consulted to assist with this decision. 3. Patients with psychotic depression. Patients who develop a depression with psychotic symptoms (delusions or hallucinations) should be evaluated by the team psychiatrist. Their treatment will likely require treatment with both an antidepressant and an antipsychotic agent. Psychotic patients may also require brief hospitalization for safety and clinical stabilization. 4. Patient with bipolar depression: While the model is not designed for patients who have been treated for bipolar disorder, it is possible that some depressed patients will actually be bipolar. Such patients can present with severe depression, a mixed manic and depressive state, or a depression that is followed by a manic state. Some depression treatments such as ECT or antidepressants may, in fact, precipitate a manic episode. When a PCP suspects that a patient is experiencing symptoms of mania, the psychiatrist should be asked to evaluate the patient. Appropriate treatment of such a patient may require the use of mood stabilizers, ECT, or temporary hospitalization for safety and stabilization.
Seven Key Challenges in Managing Depression
1. 2. 3. 4. 5. 6. 7. Make a diagnosis. Educate and recruit the patient as a partner in treatment. Start with the best possible treatment. Avoid minor tranquilizers. Use antidepressants or psychotherapy. Use an adequate dose. Treat long enough. (Patients often take 6 to 10 weeks to respond.) Follow outcomes and adjust treatment as needed. Consider consultation if patient is not improving. Prevent relapse. (50% risk after one episode, 70% after two episodes and 90% after three episodes.)

A. Diagnosing Depression in Primary Care Signs and Symptoms of Depression

Depressed mood and/or loss of interest or pleasure Sadness, tearfulness, guilt, pessimism, sense of failure, self-dislike, dissatisfaction, irritability, social withdrawal, self-harm, apathy, lack of pleasurable activities. Physical/vegetative symptoms Trouble sleeping or sleeping too much (includes early morning awakening), trouble concentrating, decreased energy, decreased sexual interest, loss of appetite, overeating, digestive problems, constipation, bowel irregularities, aches and pains Physical/vegetative signs Disheveled appearance, difficulty sitting still, restlessness, slowed speech, movements and reactions.

B.

Conditions Characterized by Depressive Symptoms

(1)

MAJOR DEPRESSION

Diagnostic Criteria for Major Depression (DSM-5)

Major depression is present when the patient has had 5 or more symptoms listed below during the same two week period and represents a change from normal functioning. One of the symptoms must be either item 1 or 2. *Do not include symptoms that are clearly attributable to another medical condition. The symptoms must cause clinically significant distress or impairment in social, occupational or other important areas of functioning. 1. 2. Depressed mood OR Loss of interest or pleasure 3. Significant change in weight or appetite 4. Insomnia or hypersomnia nearly every day 5. Psychomotor agitation or retardation nearly daily 6. Fatigue or loss of energy nearly every day 7. Feelings of worthlessness or inappropriate guilt 8. Diminished ability to think or concentrate or indecisiveness nearly every day 9. Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

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(2)

DYSTHYMIA

Diagnostic Criteria for Persistent Depressive Disorder (Dysthymia) (DSM-5)300.4(F34.1)

1. Patients with Dysthymia/Chronic Depression are in a depressed mood: for most of the day for more days than not for at least 2 years with lapses lasting not more than 2 months 2. During periods of depression*, the patient has had two or more of these symptoms: loss of self-esteem insomnia or hypersomnia feelings of hopelessness poor concentration or difficulty making decisions low energy or fatigue poor appetite or overeating
TREATMENT: Dysthymia / Chronic depression can usually be tre ated the same as major depression, except that the patient will require a full dose of medication for at least 2 years (maintenance therapy).
* Not including episodes of mania or depression relating to substance abuse. Can coexist with episodes of major depression.

Note**Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individuals history and the cultural norms for the expression of distress in the context of loss. In distinguishing grief from a major depressive episode, it is useful to consider that in grief the predominant affect is feelings of emptiness and loss, while in MDE it is persistent depressed mood and the inability to anticipate happiness or pleasure. In grief, self-esteem is usually preserved, whereas in MDE feelings of worthlessness and self-loathing are common. If a bereaved individual thinks about death and dying, such thoughts are generally focused on the deceased and possibly about joining the deceased, whereas in MDE such thoughts are focused on ending ones own life because of feeling worthless, undeserving of life, or unable to cope with the pain of depression(DSM-5).

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C.

Guidelines for Using Antidepressant Medications

(1) Antidepressant Medication Dosing a. Serotonin Reuptake Inhibitors (SSRIs)

Common side effects in all SSRIs (> 10 %): insomnia, restlessness, agitation, fine tremor, GI distress (nausea, headache, dizziness, sexual dysfunction.
Unit doses available (in Drug Name 1. Fluoxetinea 2. Paroxetinea mg) 10, 20,40 10, 20,30,40 10,20,40 12.5, 25,37.5 10,20, 40 25, 50, 100 5,10, 20 Therapeutic dosage range (mg) 10-80 10-60 40mg 25-50 10-40 25-200 10-20 20 qd 20 qd 10mg 25 qd 20 qd 50 qd 10 qd Dry mouth.Relatively few drug interactions. Also useful for PTSD and PMDD Few drug interactions, usually well tolerated $4 Fluoxetine has a very long half life. Dry mouth, constipation, weakness/fatigue Low sexual side effects and weight gain risk Starting dose in patients (mg) Comments and common side effects-specific to this drug in addition to Usual Cost common side effects described above $4=4 dollar list $4 $4 $$ no generic

3. Viibryd
4.Paroxetine CR 5. Citalopram* 6. Sertraline* 7. Escitalopram*
a

Available as a generic.

b. Other

Antidepressantsa
Unit doses available (in mg) 100,150, 200 Therapeutic dosage range (mg) 150400mg day 50-100 100-150 bid (SR) 75-225 75-225 XR 75 XR 150 30,60 qd (XR) 30 60 mg 60 mg qd 15 30 qhs Usual dose (mg) 200mg BID Starting Comments and common side effects-specific to this drug dose in patients (mg) 150mg Insomnia/agitation. QAM Also useful for smoking cessation Risk of seizures at high dosesb $$ no generic (usually must fail another SNRI first) Once or twice daily dosing with SR preparation. Slow release preparation allows once / daily dosing

Drug Name
1. Bupropion SR

2. Pristiq SR Bupropion 3.Venlafaxine XR

50,100 SR100, SR150 XR 37.5

100-150 50mg bid (SR)

50mg 100 qd (SR) 37.5 qd (XR)

4. Duloxetine*

30 mg qd Nausea, somnolence, headache, dry mouth, tremor. May be helpful for neuropathic pain and stress urinary incontinence. **now generic 15 qhs Sedation, weight gain, appetite. Enteric coated. Do not increased break tablets.

5. Mirtazapine*

15, 30

15 45 qhs

Available as generic. Bupropion should be avoided in patients with a history of seizures or with significant head trauma or CNS lesions that put the patient at higher risk for seizures.

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c.

Secondary Amine Tricyclics (TCAs)a, b, c

Common side effects in all TCAs (> 10 %): arrhythmias (particularly with preexisting b conduction defects) , dry mouth, constipation, blurry vision, orthostatic hypertension, and weight gain. All TCAs are available in generic preparations.
Unit doses available (in mg) Therapeutic dosage range (mg) 50-150 Usual dose (mg) 50-100 Starting dose in patients (mg) Comments and common side effects-specific to this drug (in addition to common side effects listed above)
Weakness/fatigue, may be helpful for pain, monitor therapeutic drug levels just before next dose Tachycardia, insomnia / agitation , Avoid abrupt withdrawal

Drug Name

1. Nortriptyline 10, 25, 50,

75

25-50mg

2. Desipramine 10, 25, 50,

75, 100,150
a

75-200

100-200

25

Tertiary amine tricyclic medications such as amitriptyline (Elavil), doxepin, or imipramine are to be avoided in older adults because of high rates of potentially harmful side effects. These medications are to be avoided in patients with a recent history of myocardial infarction or with preexisting cardiac conduction defects (1st or 2nd degree heart block), urinary retention, or narrow angle glaucoma. Serum levels are useful IF patients dont have a response at a therapeutic dose or if patients have significant side effects at very low doses (see titration schedule for recommended serum levels).

(2)
Name Nortriptyline Desipramine Fluoxetine Citalopram Escitalopram Paroxetine Sertraline

Titrating Commonly Used Antidepressants

Starting dose in mg 25-50 qhs 25 qam 20mg qam 20mg qam 10 qam 10 qpm 50 qpm Increase as needed and as tolerated (doses in mg / day) Increase by 25-50mg/day Q2-3days Increase by 25-50 mg / week May increase dose after several weeks Increase to 40 mg after 1 wk Increase to 20 mg after 1 wk Increase to 20 mg after 1 wk To 30 mg after 4 wks May increase by 25To 40 mg after 6 wks 50mg/day/week, max 200mg day Increase after 3 days. Max 150mg/dose up to 450 mg day Increase to 150 bid after 3 days, max 400mg day Increase to 75 after 1 wk to 150 tid after 6 wks to 150 mg after 3 wks Increase to mg 30 qhs 3 wks to 225 afterafter 6 wks To 45 qhs after 6 wks Increase to 60 mg qd after 1-2 wks as tolerated High / target c doses 75-150
a b

150-300 40-80 40 20 40-50

150-200

Bupropion

100mg BID

450

Bupropion SR Venlafaxine XR

150 qam 37.5 qam

400 225

Mirtazapine Duloxetine

15 qhs 30 mg qpm

45 60

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(3)

Guidelines for Switching Antidepressants

Abrupt discontinuation of short acting antidepressants can lead to an uncomfortable antidepressant withdrawal syndrome. The following is a rough guide to switching antidepressants.

Switching from SSRI to SSRI:

One can usually switch from one SSRI to another without much difficulty.

Switching from SSRI or SNRI to TCA:

Fluoxetine may be abruptly discontinued. TCAs should be increased slowly as the remaining fluoxetine may increase TCA levels. Other SSRIs or SNRIs should be tapered over 1-2 weeks in small increments. A TCA may be started and increased slowly as the SSRI or SNRI is discontinued.

Switching from TCA to SSRI:

SSRIs can significantly increase the blood levels of TCAs. Therefore, one should taper a TCA over 1-2 weeks by increments of 25-50 mg q 2-3 days. An SSRI can be started when the dose of a TCA has been significantly reduced or after the TCA is tapered off completely.

(4)

Pooled Rates of TCA and SSRI Antidepressant Side Effects across Clinical Trialsa
SSRI rate TCA rate Rate difference 10 % 3% 7% -4% - 12 % - 11 % - 30 % -4% -5% 95 % CI

Adverse effect Adverse effects more common in SSRIs Diarrhea Headache Insomnia Adverse effects more common in TCAs Blurred vision Constipation Dizziness Dry mouth Tremors Urinary disturbance

12 % 15 % 13 % 6% 8% 8% 18 % 7% 3%

3% 11 % 6% 10 % 21 % 19 % 48 % 11 % 8%

0.53 to 0.13 0.002 to 0.04 0.32 to 0.08 -0.05 to -0.01 -0.14 to -0.07 -0.13 to -0.06 -0.33 to -0.23 -0.05 to -0.01 -0.08 to -0.01

Strategies for Managing Antidepressant Side Effects

a. General Strategies: 1. Explore whether the side effects are physical or psychological? 2. Wait and support. Many side effects (i.e., GI distress with SSRIs) will subside over 1- 2 weeks of treatment. 3. Lower the dose (temporarily). 4. Treat the side effects (see below). 5. Change to a different antidepressant.

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b. Treatment Strategies for Specific Side Effects: Sedation - Give medication at bedtime - Try caffeine Orthostatic hypotension - Consider switching to a different antidepressant - Adequate hydration /dizziness - Sit-stand-get up slowly - Support hose - Consider switching to a different antidepressant Anticholinergic (dry - Hydration mouth/eyes, constipation, - Sugarless gum/candy urinary retention, - Dietary fiber tachycardia) - Artificial tears - Bethanechol 10 20 mg bid tid - For confusion stop medication and rule out other causes GI distress / nausea - This often improves or resolves over 1-2 weeks - Take with meals - Consider antacids or H2 blockers Activation / jitters / tremors - Start with small doses (especially with underlying anxiety disorder) - Reduce dose - Try beta blocker (propranolol 10 20 mg bid / tid) - Consider short term trial of benzodiazepine Headache - Lower dose - Try acetaminophen Insomnia - Trazodone 25 100 mg po qhs (can cause orthostatic hypotension and priapism) - Make sure activating antidepressants are taken in a.m.(Effexor) Sexual dysfunction - May be part of depression or medical disorders - Consider switch to bupropion, nefazodone, or mirtazapine - Decrease dose - Try adding bupropion 75 mg qhs or bid - Try adding buspirone 15-30 mg bid - Try adding cyproheptadine 4 mg 1-2 hrs before intercourse - Consider a trial of sildenafil, tadalafil, or vardenafil in consultation with PCP or urologist (5) Antidepressant Drug Interactions All antidepressants are metabolized by the P450 isoenzyme system in the liver. Certain antidepressants inhibit specific subtypes of P450 enzymes and this may increase blood levels in patients who are taking other medications metabolized by the same isoenzyme systems.
Care is advised in patients who are taking medications with a narrow therapeutic window such as tricyclic antidepressants, digoxin, warfarin, anticonvulsants, or theophylline. It is advised to observe clinically for side effects from such medications and to recheck serum blood levels of such medications as the dose of the antidepressant is titrated upwards. For example, patients who are taking both a tricyclic antidepressant and an SSRI should have their serum levels of the TCA checked in order to avoid toxicity resulting from increased levels of TCAs.

15 Some of the absolute contraindications for combining drugs involve the combination of Nefazodone with other drugs that are metabolized by the P450 3A4 enzyme system. Monoamine oxidase inhibitors (MAOIs such as phenelzine or tranylcypromine) should NOT be co-administered with other antidepressants, lithium, meperidine, stimulants, pseudoephedrine, phenylephrine, reserpine, sumatriptan, l-dopa, tyramine, or morphine. Consult with the team psychiatrist before using MAOIs as these medications have a narrow therapeutic window and can result in serotonin syndrome or hypertensive crises if used incorrectly.
Please refer to the medication package insert, a pharmacology text, or consult with your team psychiatrist or a pharmacist if you have questions about specific drug- drug interactions involving antidepressants.

(6)

Troubleshooting: What to Do if Patients Dont Improve as Expected

Possible Solution
Reconsider diagnosis and differential diagnosis Consider psychiatric consultation Increase dose Support and encourage patient to stay on medication for a full trial (8-10 weeks) at a therapeutic dose. Try to understand the patients perspective and concerns Address barriers to adherence and problem-solve together Consider serum drug levels if using tricyclic antidepressants Wait and reassure patient - the body often gets used to them (e.g., GI side effects from SSRIs or SNRIs) Reduce dose Treat side effect(s) Change medication See Strategies for Managing Antidepressant Side Effects section 5(F5)

Common problem
1. Wrong diagnosis 2. Insufficient dose 3. Insufficient length of treatment (Remember: it may take 8-10 weeks for patients to respond to treatment) 4. Problems with adherence

5. Side effects (Remember: side effects may be physiological or psychological)

6. Other complicating factors a. psychosocial stressors / barriers b. medical problems / medications c. psychological barriers (low self esteem, guilt, unwillingness to let go of sick role) d. active substance abuse e. other psychiatric problems 7. Treatment is not effective despite adequate trial of medication at adequate dose

Address problems directly Consider psychiatric consultation Consider adding psychotherapy Psychiatric consultation for difficult to treat depression

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Patient Health Questionnaire (PHQ-9)

Over the last 2 weeks, how often have you been bothered by any of the following problems? Circle the response that fits you for each question.

Not at all

Several days 1

More than half the days 2

Nearly every day 3

1) Little interest or pleasure in doing things.

2) Feeling down, depressed, or hopeless.

3) Trouble falling or staying asleep or sleeping too much.

4) Feeling tired or having little energy.

5) Poor appetite or overeating.

6) Feeling bad about yourself - or that you are a failure or have let yourself or your family down. 7) Trouble concentrating on things, such as reading the newspaper or watching television.

8) Moving or speaking so slowly that other people could have noticed? Or the opposite being so fidgety or restless that you have been moving around a lot more than usual. 9) Thoughts that you would be better off dead or of hurting yourself in some way. ADD EACH COLUMN

Adapted from Kroenke K, Spitzer RL, Williams JB: The PHQ-9: validity of a brief depression severity measure. Journal of General Internal Medicine 16:606-13, 2001.

PHQ-9 total score:

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