In our 20th episode we try to answer our accumulating listener mail. We review questions around cardiovascular disease risk-benefits and try to demystify the calculators. Listeners question antidepressants: when they should start to work, when to change dose/type and their use for chronic pain. Other issues include stopping bisphosphonates, addressing the placebo effect and uncertainties with industry funded trials. In the end, Mike talks about Giraffes and James becomes spastic.

Show Notes

1) Meta-analysis data for mortality benefit with statins in primary prevention

TI meta-analysis on statins in women for primary prevention.

“For women without cardiovascular disease, lipid lowering does not affect total or CHD mortality. Lipid lowering may reduce CHD events, but current evidence is insufficient to determine this conclusively.”

JAMA 2004;291:2243-52

2) Don’t change the doses of antidepressants too quickly

Br J Psyc 2006;189:309–16

3) How quickly do antidepressants work?

Arch Gen Psyc 2006; 63: 1217-23. (for how fast anti-depressants work)

4) How long do we use bisphosphonates?

N Engl J Med 2004;350:1189–1199

JAMA 2006;296:2927-38

Options in treatment, which ones have evidence of non-vertebral fracture and the absolute benefits of those treatments. We discuss reliability of monitoring bone density of patients on therapy and the duration of therapy.

Show Notes

1) Evidence for fracture reduction

There is good evidence from randomized controlled trials (RCTs) that alendronate, etidronate, ibandronate, risedronate, calcitonin, 1-34 PTH, and raloxifene prevent vertebral fractures compared with placebo.

There is good evidence from RCTs that risedronate and alendronate prevent both nonvertebral and hip fractures compared with placebo.

There is good evidence that zoledronic acid prevents vertebral and nonvertebral fractures, and fair evidence that it prevents hip fractures.

Agency for healthcare research and quality – report

2) Calcitonin appears to be effective in the management of acute pain associated with acute osteoporotic vertebral compression fractures by shortening time to mobilization

Osteoporosis Int 2005;16:1281-90

3) Relative and absolute benefits from using alendronate for 2-3 years

Approximately

45% reduction in vertebral fractures – 2% absolute reduction for primary and 6% for secondary

20% reduction in non-vertebral – just secondary prevention – 2% absolute reduction

50% reduction in hip fractures – just secondary prevention – 1% absolute reduction

Cochrane Library

In episode 18 we consider the approach to questions of bone density and fracture risk. We use a series of cases to work through the risk of osteoporosis (using a simple tool) and help us decide on bone mineral density testing. We discuss initial options in the prevention of fractures including weight-bearing exercise, Calcium and Vitamin D (and its additional advantages).

Show Notes

1) Osteoporosis self-assessment tool – estimating risk of osteoporosis

2) Vitamin D and Calcium (for fracture)

3) Vitamin D and falling risk

JAMA 2004;291:1999-2006

4) Meta-analysis of Vit D on Mortality

Arch Intern Med 2007;167:1730-1737

In episode 17 we look at managing the treatment of depression once we’ve started a medication. We discuss the patient conversations necessary for initiating treatment including the patient perception of the illness, expectations and potential side-effects. We debate the quandaries around starting doses, when or if to increase, duration of therapy and relapse prevention. Although we use available evidence, we acknowledge some of our advice is Best-Guess based medicine.

Show Notes

1) Monitoring form for using antidepressants in children and adolescents

2) Clinical tool to monitor antidepressant treatment

3) Scales, doctors finding benefit (when there isn’t any)

Lancet 2004;363:1341-5

4) Investigators’ conclusions on the efficacy of newer antidepressants in childhood depression have exaggerated their benefits

BMJ 2004;328:879-83

5) Benefit seen in 1 week with antidepressants

Arch Gen Psychiatry 2006;63:1217-23

6) The risk of recurrence progressively increases with each successive episode and decreases as the duration of recovery increases

Am J Psychiatry 2000;157:229–233)

7) Relapse due to stopping meds – relapse at 12 months – 18% on drugs 41% on placebo

Lancet 2003;361:653–51

8) 5mg of fluoxetine works Psychopharmacology Bulletin 1988;24:183-8

Click here to download article

In episode 16 we look at initiating treatment for depression. We briefly review screening and the diagnosis of depression before discussing the non-drug treatment options (therapy, exercise, sleep hygiene). We search for the anti-depressant of choice (being any) and end up deciding to tailor the choice based on factors such as side-effect profile, targeted symptoms, and cost. Although we stress the importance of regular follow-up, James refuses to come to see Mike or Adil.

Show Notes

1) Two screening questions for depression – do you feel depressed, do you have little interest in doing things

BMJ 2003; 327:1144-46

J Gen Intern Med. 1997;12:439-45

2) Benefit seen in 1 week with antidepressants

Arch Gen Psychiatry 2006;63:1217-23

3) No difference between the second generation antidepressants in effect

Ann Intern Med. 2005;143 :415-26

4) Weight benefit with fluoxetine.

Arch Intern Med 2004;164:1395-1404

5) Amitriptyline is as effective as other tricyclics or newer agents

Cochrane Library

6) Monitoring form for using antidepressants in children and adolescents

7) Clinical tool to monitor antidepressant treatment

In episode 15 a guest assists us in addressing the evidence suggesting anti-depressants are not as effective as believed. We review some biases in the anti-depressant research including publication bias (how good studies are published more than bad studies). We discuss how the benefits of anti-depressants over placebo increase as the severity of depression worsens. James prompts us to explain the effectiveness of the medications; although we dodge, some vague commitments do manage to escape.

Show Notes

1) Selective publication of selective serotonin reuptake inhibitors data

BMJ 2003;326:1171-73

2) Another select report on the selective publication of selective serotonin reuptake inhibitors

NEJM 2008; 358: 252

3) Antidepressants have a clinically important effect above placebo only in patients with severe depression

PLOS 2008:5(2):0260-8

4) Fluoxetine – evidence for benefit in children – others maybe not?

Lancet 2004;363:1341-5

5) In children, with antidepressants, the magnitude of benefit is unlikely sufficient to justify the harms

http://www.bmj.com/cgi/content/full/328/7444/879

In episode 14 we attempt to answer some of the mail received from listeners. We talk about using the evidence to promote shared decision-making. We review calculating risk, the limitations of risk calculators and presenting the data in the positive (chance of not having an event). We address heart disease as the leading cause of mortality (despite advancement in treatment) and emerging discussions of statin use in children (age ?8). We unwrap these enigmas to create more confusion.

Show Notes

1) Some references showing high cholesterol in patients over age 75-80 is not necessarily associated with increased mortality or sometimes not even increased cardiovascular disease.

Ann Epidemiol 2004;14:705–21

JAMA 1994;272:1335-40

Ann Int Med 1997;126:753-60

J Am Geriatr Soc 2004;52:1639-47

Arch Int Med 2003;163:1549-54

J Am Geriatr Soc 2005;53:2159-64

J Am Geriatr Soc 2005;53:219-26

2) Treatment of hypertension in patients 80 years of age or older reduces the chance of a cardiovascular event by 3% over 2 years

NEJM 2008;358:1887-98

In our 13th episode, we discuss smoking cessation. We present the impressive benefits in hard outcomes when people stop smoking. We then go through the list of interventions, from brief advice to the pharmaceutical options of nicotine replacement, two anti-depressants (Buproprion or Nortiriptyline) and the newest agent, Varenicline. Dosing, cessation rates and adverse events are reviewed (for medications, not cigarettes: that dose is zero).

Show Notes

1) Intensive smoking cessation intervention reduces mortality in high-risk smokers with cardiovascular disease

Chest 2007; 131: 446–52.

2) Listening empathetically and asking if they are ready to quit smoking

Silagy C, Ketteridge S. The effectiveness of physician advice to aid smoking cessation. Cochrane Database of Systematic Reviews 1998. Issue 2

3) Bupropion at a dose of 150 mg daily works as well as 300 mg daily

New Engl J Med 1997; 337:1195-202

4) Nortriptyline and bupropion for smoking cessation

Antidepressants for smoking cessation. Cochrane Database of Systematic Reviews 2007, Issue 1

5) Varenicline for smoking cessation

Nicotine receptor partial agonists for smoking cessation. Cochrane Database of Systematic Reviews 2008. Issue 3

In our 12th episode, we divide and conquer the remaining points around hypertension. In section A, we talk about monitoring blood pressure: frequency, reliability and home monitoring are all discussed. In section B, we talk about the potential side-effects of different hypertension therapies and the need to monitor for biochemical-metabolic effects. In the end, Mike is hyper and James is tense but both need therapy.

Show Notes

1) Effect of home blood pressure monitoring on blood pressure

BMJ 2004;329:145

2) Hypokalemia and metabolic effects of thiazides are dose related

BMJ 1990;300:975

3) Cardioselective beta-blockers in mild-moderate asthma and COPD Cardioselective beta-blockers in asthma

Ann Intern Med. 2002;137:715-725

Cardioselective beta-blockers in COPD

Cochrane library

Other resources

• Beta-Blockers in Asthma (Ann-Intern-Med, 2003)
• Beta-Blockers in COPD (cochrane, 2005)
• Meta-analysis of home BP monitoring (BMJ, 2004)

In our 11th episode, we discuss the laundry list of the remaining hypertensive medications and their evidence. The issue of blood pressure as a surrogate marker is discussed and we encourage clinicians to focus on hypertensive agents that effect patient oriented outcomes. While the evidence is reasonable for Ca+ Blocker, we put Beta-blockers low down (and Atenolol off) the list with Alpha-blockers and a few others.We have few laughs along the way, primarily at our lack of humor.

Show Notes

1) Atenolol no better than placebo and other drugs are better than atenolol in reducing cardiovascular outcomes in patents with high blood pressure

Lancet 2004;364:1684–9

2) Beta-blockers do appear to increase the chance of developing diabetes

Am J Cardiol 2007;100:1254–62

3) A debate on using or not using betablockers for high blood pressure

Can Fam Physician 2007;53:614-7

4) ALLHAT – the problem with alpha-blockers

JAMA 2000;283:1967-75

5) Data for felodipine and cardiovascular events in patients with high blood pressure

Lancet 1998;351:1755-62

6) Use of low-dose spironolactone in “resistant” hypertension

Amer J Hyper 2003;16:925–30

7) Effect of spironolactone on albuminuria

Diabetes Care 2005;28:2106–12